We thank Dr. John Greaves and Ms. Soroosh Sorooshian, Department of Chemistry, University of California, Irvine Mass Spectrometry Facility, for mass spectrometric analyses. We also thank Mr. Jacob Buchanan for helpful discussions, as well as Miss Stephanie J. Conn, Mrs. Shannon M. Huffman (Vreeland), and Miss Alexandra N. Wexler for early stage work on this project. Partial funding was provided by the Central Washington University (CWU) School of Graduate Studies (C.E.M), the CWU Seed Grant Program, and the CWU Faculty Research Program.

<ol><li>Adabala, P. J. P., Legresley, E. B., Bance, N., Niikura, M., Pinto, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Exploitation+of+the+Catalytic+Site+and+150+Cavity+for+Design+of+Influenza+A+Neuraminidase+Inhibitors%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Exploitation of the Catalytic Site and 150 Cavity for Design of Influenza A Neuraminidase Inhibitors.</a> J. Org. Chem. 78 (21), 10867-10877 (2013).</li>
<li>Trost, B. M., Kaneko, T., Andersen, N. G., Tappertzhofen, C., Fahr, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Total+Synthesis+of+Aeruginosin+98B%5BTitle%5D)+AND+%22J.+Am.+Chem.+Soc%22%5BJournal%5D)">Total Synthesis of Aeruginosin 98B.</a> J. Am. Chem. Soc. 134 (46), 18944-18947 (2012).</li>
<li>Conn, S. J., Vreeland, S. M., Wexler, A. N., Pouwer, R. H., Quinn, R. J., Chamberland, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Total+Synthesis+of+Clavatadine%5BTitle%5D)+AND+%22A.+J.+Nat.+Prod%22%5BJournal%5D)">Total Synthesis of Clavatadine.</a> A. J. Nat. Prod. 78, 120-124 (2014).</li>
<li>Buchanan, J. C., Petersen, B. P., Chamberland, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Concise+Total+Synthesis+of+Phidianidine+A+and+B%5BTitle%5D)+AND+%22Tetrahedron+Lett%22%5BJournal%5D)">Concise Total Synthesis of Phidianidine A and B.</a> Tetrahedron Lett. 54, 6002-6004 (2013).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Technical+Bulletin+AL-134%3A+Handling+Air-Sensitive+Reagents%22">Technical Bulletin AL-134: Handling Air-Sensitive Reagents</a>. , at: 
	
 <a target="_blank" href="http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Aldrich/Bulletin/al_techbull_al134.pdf">http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Aldrich/Bulletin/al_techbull_al134.pdf</a> (2012).</li>
<li>Castagnolo, D., Raffi, F., Giorgi, G., Botta, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Macrocyclization+of+Di-Boc-guanidino-alkylamines+Related+to+Guazatine+Components%3A+Discovery+and+Synthesis+of+Innovative+Macrocyclic+Amidinoureas%5BTitle%5D)+AND+%22Eur.+J.+Org.+Chem%22%5BJournal%5D)">Macrocyclization of Di-Boc-guanidino-alkylamines Related to Guazatine Components: Discovery and Synthesis of Innovative Macrocyclic Amidinoureas.</a> Eur. J. Org. Chem. 2009 (3), 334-337 (2009).</li>
<li>Zubrick, J. W. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aZubrick%2C+JW+%22The+Organic+Chem+Lab+Survival+Manual%3A+A+Student%27s+Guide+to+Techniques%22">The Organic Chem Lab Survival Manual: A Student's Guide to Techniques</a>. , Wiley. Hoboken. (2012).</li>
<li>Pirrung, M. C. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aPirrung%2C+MC+%22The+Synthetic+Organic+Chemist%27s+Companion%22">The Synthetic Organic Chemist's Companion</a>. , Wiley-Interscience. Hoboken, N.J. (2007).</li>
<li>Padias, A. B. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aPadias%2C+AB+%22Making+the+Connections+2%3A+A+How-To+Guide+for+Organic+Chemistry+Lab+Techniques%2C+Second+Edition%22">Making the Connections 2: A How-To Guide for Organic Chemistry Lab Techniques, Second Edition</a>. , Hayden-McNeil Publishing. Plymouth, MI. (2011).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques+Manual%3A+Volumetric+Techniques%22">Digital Lab Techniques Manual: Volumetric Techniques</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/volumetric-techniques/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/volumetric-techniques/</a> (2007).</li>
<li>Baker, T. J., Tomioka, M., Goodman, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Preparation+and+Use+of+N%2CN%27-Di-Boc-N%26%2334%3B-Triflylguanidine%5BTitle%5D)+AND+%22Org.+Synth%22%5BJournal%5D)">Preparation and Use of N,N'-Di-Boc-N&#34;-Triflylguanidine.</a> Org. Synth. 78, 91-98 (2002).</li>
<li>Baker, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthesis+of+Biologically+Important+Guanidine-Containing+Molecules+Using+Triflyl-Diurethane+Protected+Guanidines%5BTitle%5D)+AND+%22Synthesis%22%5BJournal%5D)">Synthesis of Biologically Important Guanidine-Containing Molecules Using Triflyl-Diurethane Protected Guanidines.</a> Synthesis. S1, 1423-1426 (1999).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques%3A+Using+a+Balance%22">Digital Lab Techniques: Using a Balance</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/using-a-balance/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/using-a-balance/</a> (2007).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques%3A+Reaction+Work-Up+I%3A+Extraction%2C+Washing%2C+and+Drying%22">Digital Lab Techniques: Reaction Work-Up I: Extraction, Washing, and Drying</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/reaction-work-up-i/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/reaction-work-up-i/</a> (2007).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques%3A+Filtration%22">Digital Lab Techniques: Filtration</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/filtration/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/filtration/</a> (2007).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques%3A+Reaction+Work-Up+II%3A+Using+the+Rotovap%22">Digital Lab Techniques: Reaction Work-Up II: Using the Rotovap</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/reaction-work-up-ii/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/reaction-work-up-ii/</a> (2007).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques%3A+Column+Chromatography%22">Digital Lab Techniques: Column Chromatography</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/column-chromatography/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/column-chromatography/</a> (2007).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Flash+Chromatography+101%22">Flash Chromatography 101</a>. , Available from: 
 <a target="_blank" href="https://www.youtube.com/watch?v=fF1gXUvyGb4">https://www.youtube.com/watch?v=fF1gXUvyGb4</a> (2015).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22Digital+Lab+Techniques+Manual%3A+TLC+-+The+Basics%22">Digital Lab Techniques Manual: TLC - The Basics</a>. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/tlc-the-basics/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/tlc-the-basics/</a> (2007).</li>
<li>Digital Lab Techniques: TLC - Advanced. , MIT OpenCourseWare. at 
 <a target="_blank" href="http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/tlc-advanced/">http://ocw.mit.edu/resources/res-5-0001-digital-lab-techniques-manual-spring-2007/videos/tlc-advanced/</a> (2007).</li>
<li>Massachusetts Institute of Technology Department of Chemistry Instrumentation Facility. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22NMR+Tips+and+Tricks%22">NMR Tips and Tricks</a>. , Massachusetts Institute of Technology. Cambridge, Massachusetts, USA. Available from: 
 <a target="_blank" href="http://web.mit.edu/speclab/www/tips.htm">http://web.mit.edu/speclab/www/tips.htm</a> (2015).</li>
<li>Krohn, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthese+des+Bactereostatischen+2.4-Dibrom-homogentisins%C3%A4ure+-+Amids+und+Verwandter+Verbindungen%5BTitle%5D)+AND+%22Tetrahedron+Lett%22%5BJournal%5D)">Synthese des Bactereostatischen 2.4-Dibrom-homogentisinsäure - Amids und Verwandter Verbindungen.</a> Tetrahedron Lett. 16 (52), 4667-4668 (1975).</li>
<li>Wolkowitz, H., Dunn, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Homogentisic+Acid%5BTitle%5D)+AND+%22Biochem.+Prep%22%5BJournal%5D)">Homogentisic Acid.</a> Biochem. Prep. 4, 6-11 (1955).</li>
<li>Feichtinger, K., Zapf, C., Sings, H. L., Goodman, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Diprotected+Triflylguanidines%3A+A+New+Class+of+Guanidinylation+Reagents%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Diprotected Triflylguanidines: A New Class of Guanidinylation Reagents.</a> J. Org. Chem. 63, 3804-3805 (1998).</li>
<li>Ariza, X., Urpì, F., Vilarrasa, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+practical+procedure+for+the+preparation+of+carbamates+from+azides%5BTitle%5D)+AND+%22Tetrahedron+Lett%22%5BJournal%5D)">A practical procedure for the preparation of carbamates from azides.</a> Tetrahedron Lett. 40, 7515-7517 (1999).</li>
<li>Ariza, X., Urpì, F., Viladomat, C., Vilarrasa, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((One-Pot+Conversion+of+Azides+to+Boc-Protected+Amines+with+Trimethylphosphine+and+Boc-ON%5BTitle%5D)+AND+%22Tetrahedron+Lett%22%5BJournal%5D)">One-Pot Conversion of Azides to Boc-Protected Amines with Trimethylphosphine and Boc-ON.</a> Tetrahedron Lett. 39, 9101-9102 (1998).</li>
<li>Snider, B. B., Song, F., Foxman, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Total+Syntheses+of+%28%C2%B1%29-Anchinopeptolide+D+and+%28%C2%B1%29-Cycloanchinopeptolide%5BTitle%5D)+AND+%22D.+J.+Org.+Chem%22%5BJournal%5D)">Total Syntheses of (±)-Anchinopeptolide D and (±)-Cycloanchinopeptolide.</a> D. J. Org. Chem. 65 (3), 793-800 (2000).</li>
<li>Barykina, O., Snider, B. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthesis+of+%28%2B-%29-Eusynstyelamide+A%5BTitle%5D)+AND+%22Org.+Lett%22%5BJournal%5D)">Synthesis of (+-)-Eusynstyelamide A.</a> Org. Lett. 12 (11), 2664-2667 (2010).</li>
<li>Yu, M., Pochapsky, S. S., Snider, B. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthesis+of+%28%C2%B1%29-Bistellettadine+A%5BTitle%5D)+AND+%22Org.+Lett%22%5BJournal%5D)">Synthesis of (±)-Bistellettadine A.</a> Org. Lett. 12 (4), 828-831 (2010).</li>
<li>Expòsito, A., Fernández-Suárez, M., Iglesias, T., Muñoz, L., Riguera, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Total+Synthesis+and+Absolute+Configuration+of+Minalemine+A%2C+a+Guanidine+Peptide+from+the+Marine+Tunicate+Didemnum+rodriguesi%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Total Synthesis and Absolute Configuration of Minalemine A, a Guanidine Peptide from the Marine Tunicate Didemnum rodriguesi.</a> J. Org. Chem. 66, 4206-4213 (2001).</li>
<li>Wuts, P. G. M., Greene, T. W. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aWuts%2C+PGM+%22Greene%27s+Protective+Groups+in+Organic+Synthesis%22">Greene's Protective Groups in Organic Synthesis</a>. , John Wiley & Sons, Inc. Hoboken, New Jersey. (2007).</li>
<li>Malmberg, C. E., Chamberland, S. Total synthesis of clavatadine A analogues to produce a viable reversible inhibitor for factor XIa. 249th American Chemical Society National Meeting, March 22-26, 2015, Denver, CO, United States, , (2015).</li>
<li>Bhonde, V. R., Looper, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+Stereocontrolled+Synthesis+of+%28%2B%29-Saxitoxin%5BTitle%5D)+AND+%22J.+Am.+Chem.+Soc%22%5BJournal%5D)">A Stereocontrolled Synthesis of (+)-Saxitoxin.</a> J. Am. Chem. Soc. 133, 20172-20174 (2011).</li>
<li>Lin, H. Y., Snider, B. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Synthesis+of+Phidianidines+A+and+B%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Synthesis of Phidianidines A and B.</a> J. Org. Chem. 77, 4832-4836 (2012).</li>
<li>Hickey, S. M., Ashton, T. D., Pfeffer, F. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Facile+Synthesis+of+Guanidine+Functionalised+Building+Blocks%5BTitle%5D)+AND+%22Asian+J.+Org.+Chem%22%5BJournal%5D)">Facile Synthesis of Guanidine Functionalised Building Blocks.</a> Asian J. Org. Chem. 4 (4), 320-326 (2015).</li>
<li>Looper, R. E., Haussener, T. J., Mack, J. B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Chlorotrimethylsilane+Activation+of+Acylcyanamides+for+the+Synthesis+of+Mono-N-acylguanidines%5BTitle%5D)+AND+%22J.+Org.+Chem%22%5BJournal%5D)">Chlorotrimethylsilane Activation of Acylcyanamides for the Synthesis of Mono-N-acylguanidines.</a> J. Org. Chem. 76, 6967-6971 (2011).</li>
<li>Shimokawa, J., Ishiwata, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Total+Synthesis+of+%28%2B%29-Batzelladine+A+and+%28%2B%29-Batzelladine+D%2C+and+Identification+of+Their+Target+Protein%5BTitle%5D)+AND+%22Chem.+Eur.+J%22%5BJournal%5D)">Total Synthesis of (+)-Batzelladine A and (+)-Batzelladine D, and Identification of Their Target Protein.</a> Chem. Eur. J. 11, 6878-6888 (2005).</li>
<li>Katritzky, A. R., Rogovoy, B. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Recent+Developments+in+Guanylating+Agents%5BTitle%5D)+AND+%22ARKIVOC%22%5BJournal%5D)">Recent Developments in Guanylating Agents.</a> ARKIVOC. iv, 49-87 (2005).</li>
<li>Berlinck, R. G. S., Trindade-Silva, A. E., Santos, M. F. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+chemistry+and+biology+of+organic+guanidine+derivatives%5BTitle%5D)+AND+%22Nat.+Prod.+Rep%22%5BJournal%5D)">The chemistry and biology of organic guanidine derivatives.</a> Nat. Prod. Rep. 29, 1382-1406 (2012).</li>
<li>Ebada, S., Proksch, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Chemical+and+Pharmacological+Significance+of+Natural+Guanidines+from+Marine+Invertebrates%5BTitle%5D)+AND+%22Mini-Rev.+Med.+Chem%22%5BJournal%5D)">Chemical and Pharmacological Significance of Natural Guanidines from Marine Invertebrates.</a> Mini-Rev. Med. Chem. 11 (3), 225-246 (2011).</li>
</ol>

The authors have nothing to declare.

מאמצים ראשוניים להכין clavatadine גייס גישה מסורתית, עקיפת guanidinylation מ מבשר אמין מתאים, אשר במקרה זה היה יזיד סופנית. בלב המאמץ הזה היה האיחוד של שני החצאים של המולקולה לבנות מחצית carbamate. למרבה הצער, כל הניסיונות לממש הפחתה תזיד בציפיית guanidinylation בשלב מאוחר מתוכנן לא צלחו. 25...

המטרה של הווידאו הזה היא להראות כיצד בשיטת guanidinylation ישירה והתחילה לעשות מבנה guanidine מסוף הוא מעשית יותר, מהיר, ויעיל יותר מאשר שיטות מסורתיות guanidinylation בסינתזה אורגנית. הקבוצה guanidine פונקציונלי, נמצא על ארגינין חומצה אמינית, היא אלמנט מבני מפתח מוצרים רבים ותרופות טבע מורכבים. התגלית ועיצוב guanidine חדשה המכילה מוצרים טבעיים ומולקולות קטנות להקים את צורך שיטת guanidinylation יעילה יותר. הגישה העוקפת הנפוצה כולל ההקדמה של מבשר guanidine סמוי כי הוא חשף בשלב מאוחר בסינתזה. לעומת זאת, טקטיקה פשוטה מתקינה guanidine מוגן על גבי אמין עיקרי מוקדם מסלול סינטטי. אופי תגובתי של guanidines בדרך כלל מונע מהם שימוש שגרתי ללא אסטרטגיה קבוצת הגנה מתאימה. באופן מסורתי, שיטותקבוצה להוסיף guanidine תפקודית כללה גישה עקיפה שכלל צעדי הגנה מרובים ואחריו הוספת guanidine בסוף הסינתזה. שני סינתזות האחרונות ממחישות את החסרונות הגלומים 1,2 guanidinylation עקיף. השיטה ישיר דיווחה בזאת כרוכה להגיב ריאגנט guanidine מוגן עם אמין ראשוני בשלב המוקדם של הסינתזה של מולקולת נתונה ולאחר מכן deprotecting אותו בסוף של הסינתזה. אסטרטגיה זו נפרסה בהצלחה בסינתזה כוללת האחרונה של אלקלואידים ימיים פעילים ביולוגי clavatadine A A ו phidianidine ו- B 3,4. אמנם שיטת guanidinylation ישירה זה יש יתרונות על פני שיטות מסורתיות של guanidinylation זה עדיין יש חסרונות. התנאים הכימיים כי guanidine המוגן יכול לשרוד יהיה תלוי בקבוצה להגן מועסקים. למרות החסרונות הפוטנציאליים הללו, שיטת guanidinylation הישירה היא אסטרטגיה המאפשרתלהוסיף guanidines מסוף אמין ראשונית לשימוש בסינתזה של מולקולות אורגניות מורכבות.

<table><tbody><tr><td>Chloroform-d</td><td>Sigma-Aldrich</td><td>612200-100G</td><td>99.8% D, 0.05% v/v tetramethylsilane; Caution: toxic</td></tr><tr><td>Dimethylsulfoxide-d&lt;sub&gt;6&lt;/sub&gt;</td><td></td><td>185965-50G</td><td>99.9% D, 1% v/v tetramethylsilane</td></tr><tr><td>sodium thiosulfate pentahydrate</td><td>Sigma-Aldrich</td><td>S8503-2.5KG</td><td></td></tr><tr><td>sodium sulfate, anhydrous</td><td>Sigma-Aldrich</td><td>238597-2.5KG</td><td></td></tr><tr><td>silica gel</td><td>Fisher Scientific</td><td>S825-25</td><td>Merck, Grade 60, 230-400 mesh</td></tr><tr><td>washed sea sand</td><td>Sigma-Aldrich</td><td>274739-5KG</td><td></td></tr><tr><td>hexane</td><td>Sigma-Aldrich</td><td>178918-20L</td><td>Caution: flammable</td></tr><tr><td>ethyl acetate</td><td>Sigma-Aldrich</td><td>319902-4L</td><td></td></tr><tr><td>methylene chloride</td><td>Sigma-Aldrich</td><td>D65100-4L</td><td></td></tr><tr><td>sodium chloride</td><td>Sigma-Aldrich</td><td>S9888-10KG</td><td></td></tr><tr><td>sodium bicarbonate</td><td>Sigma-Aldrich</td><td>S6014-2.5KG</td><td></td></tr><tr><td>acetic acid</td><td>Sigma-Aldrich</td><td>695092-2.5L</td><td></td></tr><tr><td>hydrochloric acid</td><td>Sigma-Aldrich</td><td>258248-2.5L</td><td>Caution: Corrosive</td></tr><tr><td>bromine</td><td>Sigma-Aldrich</td><td>470864-50G</td><td>&gt;99.99% trace metals basis; Caution: Corrosive, causes severe burns</td></tr><tr><td>hydrobromic acid</td><td>Sigma-Aldrich</td><td>244260-500ML</td><td>48% aqueous; Caution: Corrosive</td></tr><tr><td>2,5-dimethoxyphenylacetic acid</td><td>ChemImpex</td><td>26909</td><td></td></tr><tr><td>chloroform</td><td>Sigma-Aldrich</td><td>132950-4L</td><td>Caution: Toxic</td></tr><tr><td>tetrahydrofuran</td><td>Sigma-Aldrich</td><td>360589-4x4L</td><td>Caution: highly flammable</td></tr><tr><td>&lt;em&gt;N,N&lt;/em&gt;-diisopropylethylamine</td><td>Sigma-Aldrich</td><td>D125806-500ML</td><td>Caution: Corrosive</td></tr><tr><td>triethylamine</td><td>Sigma-Aldrich</td><td>T0886-1L</td><td>Caution: Corrosive</td></tr><tr><td>3 Angstrom molecular sieves</td><td>Sigma-Aldrich</td><td>208574-1KG</td><td></td></tr><tr><td>calcium hydride</td><td>Sigma-Aldrich</td><td>213268-100G</td><td>Caution: Corrosive, reacts violently with water</td></tr><tr><td>ammonium molybdate</td><td>Sigma-Aldrich</td><td>431346-50G</td><td></td></tr><tr><td>phosphomolybdic acid</td><td>Sigma-Aldrich</td><td>221856-100G</td><td></td></tr><tr><td>cerium(IV) sulfate</td><td>Sigma-Aldrich</td><td>359009-25G</td><td></td></tr><tr><td>1-butanol</td><td>Sigma-Aldrich</td><td>537993-1L</td><td></td></tr><tr><td>1,4-butanediamine</td><td>Sigma-Aldrich</td><td>D13208-100G</td><td>Caution: Corrosive / warm in hot water bath to melt prior to use</td></tr><tr><td>triphosgene</td><td>VWR</td><td>200015-064</td><td>Caution: Highly Toxic</td></tr><tr><td>methanol</td><td>Sigma-Aldrich</td><td>646377-4X4L</td><td></td></tr><tr><td>sodium acetate</td><td>Sigma-Aldrich</td><td>241245-100G</td><td></td></tr><tr><td>Dimethylsulfoxide-d&lt;sub&gt;6&lt;/sub&gt;</td><td>Sigma-Aldrich</td><td>570672-50G</td><td>Anhydrous, 99.9% D</td></tr><tr><td>sodium hydroxide</td><td>Sigma-Aldrich</td><td>221465-500G</td><td>Caution: Corrosive</td></tr><tr><td>guanidine hydrochloride</td><td>Sigma-Aldrich</td><td>G4505-25G</td><td>Caution: Toxic, Corrosive</td></tr><tr><td>di-tert-butyl dicarbonate</td><td>VWR</td><td>200002-018%</td><td>Caution: Toxic / may warm in hot water bath to melt prior to use</td></tr><tr><td>trifluoromethanesulfonic anhydride</td><td>Fisher Scientific</td><td>50-206-771</td><td>98%, anhydrous; Caution: toxic, corrosive, extremely moisture sensitive</td></tr></tbody></table>

a direct, early stage guanidinylation protocol for the synthesis of complex aminoguanidine-containing natural products

קבוצת guanidine הפונקציונלית, המוצגת ביותר בהבלטת ארגינין חומצת אמינו, אחת מאבני הבניין הבסיסיים של חיים, היא מרכיב מבני חשוב נמצא הרבה מוצרים ותרופות טבע מורכבים. בשל הגילוי המתמיד של מוצרים טבעיים guanidine המכיל חדשים ומולקולות קטנות נועדו, שיטות guanidinylation מהירות ויעילות הן עניין להוט כימאים אורגניים סינטטיים מרפאים. מכיוון nucleophilicity ו הבסיסי של guanidines יכולים להשפיע טרנספורמציות כימי עוקבות מסורתי, guanidinylation העקיף הוא נרדף בדרך כלל. שיטות עקיפות להעסיק צעדי הגנה מרובים נפוצות מעורבים מבשר אמין סמוי, כגון יזיד, phthalimide, או carbamate. תוך עקיפת שיטות עוקפות אלה והעסקת תגובה guanidinylation ישירה מוקדם ברצף סינתטי, ניתן היה לזייף את guanidine מסוף לינארי המכיל עמוד השדרה של clavatadine לממשסינתזה קצרה ויעילה של מעכב שיה גורם זה חזק. בפועל, hydrochloride guanidine מעובד באמצעות מערך הגנה שנבנה בקפידה כי הוא מותאם כדי לשרוד את השלבים הסינתטיים לבוא. בעריכת א clavatadine, guanidinylation הישירה של diamine הזמין מסחרי בוטלה שני צעדים מיותרים מן הסינתזה שלה. יחד עם המגוון הרחב של קבוצות הגנת guanidine הידוע, guanidinylation הישירה הצטיינה פרקטית תמציתית ויעילות הטמון לשיטות למצוא הביתה של ארגז כלי כימאי סינטטי.

Guanidinylation הישיר של α זמין מסחרי,-diamine ω, ואחריו תגובה עם triphosgene, ספק את isocyanate תגובתי 8 כמו החלק הליניארית של clavatadine (איור 1b). תשואות של רצף תגובת שני שלבים הם תמיד גבוהות, 95% או יותר. מגיב Guanidinylation 6 הוכן בדיוק כפי שתואר על ידי גודמ...

Watch this Scientific Journal Video about A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products at JoVE.com

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

ישיר, בשלבים מוקדמים Guanidinylation פרוטוקול לסינתזה של מוצרים טבעיים Aminoguanidine המכיל קומפלקס

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

a-direct-early-stage-guanidinylation-protocol-for-synthesis-complex

Research

JoVE Journal

Chemistry

10.6K Views.  Central Washington University. Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol. 

Video: A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes &#945;v and &#945;5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (N&#969;) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N&#8242;-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

A protocol for the synthesis of alkyl-modified guanidines based on the use of the corresponding precursors is presented.

שינויו Functionalization של קבוצת guanidine ידי מבשרי תפורות

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. ...

Biochemistry

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide sequences. Synthesis of some unnatural amino acids often includes the use of a precursor consisting of a Schiff-base stabilized by a nickel cation. Unnatural side-chains can be installed on an amino acid backbone found in this Schiff-base complex. The resulting unnatural amino acid can then be isolated from this complex using hydrolysis of the Schiff-base, typically by employing reflux in strongly acidic solution. These highly acidic conditions may remove acid-labile side-chain protecting groups necessary for the unnatural amino acids to be used in microwave-assisted solid-phase peptide synthesis. In this work, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff base complex. Hydrolysis conditions presented in this work are suitable for retention of acid-labile side-chain protecting groups and may be adaptable to a variety of unnatural amino acid substrates.

Here, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff-base complex. Hydrolysis conditions presented here are suitable for use when retention of acid-labile side-chain protecting groups is required. This technique may be adaptable to a variety of unnatural amino acid substrates.

הידרוליזה של תנאי Ni-שיף-Base מורכבים באמצעות מתאים שמירת חומצה-רָפִיף קבוצות הגנה

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

פרוטוקול לסינתזה של<em&gt; Ortho</em&gt; נגזרי אנילין -trifluoromethoxylated

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. Their synthesis by conventional organic chemistry often requires tedious multi-step synthesis processes, with difficult control of the stereochemical outcome. We present a protocol to enzymatically synthetize amino alcohols starting from the readily available L-lysine in 48 h. This protocol combines two chemical reactions that are very difficult to conduct by conventional organic synthesis. In the first step, the regio- and diastereoselective oxidation of an unactivated C-H bond of the lysine side-chain is catalyzed by a dioxygenase; a second regio- and diastereoselective oxidation catalyzed by a regiodivergent dioxygenase can lead to the formation of the 1,2-diols. In the last step, the carboxylic group of the alpha amino acid is cleaved by a pyridoxal-phosphate (PLP) decarboxylase (DC). This decarboxylative step only affects the alpha carbon of the amino acid, retaining the hydroxy-substituted stereogenic center in a beta/gamma position. The resulting amino alcohols are therefore optically enriched. The protocol was successfully applied to the semipreparative-scale synthesis of four amino alcohols. Monitoring of the reactions was conducted by high performance liquid chromatography (HPLC) after derivatization by 1-fluoro-2,4-dinitrobenzene. Straightforward purification by solid-phase extraction (SPE) afforded the amino alcohols with excellent yields (93% to &#62;95%).

Chiral amino alcohols are versatile molecules for use as scaffolds in organic synthesis. Starting from L-lysine, we synthesize amino alcohols by an enzymatic cascade reaction combining diastereoselective C-H oxidation catalyzed by dioxygenase followed by cleavage of the carboxylic acid moiety of the corresponding hydroxyl amino acid by a decarboxylase.

תגובות אנזימטיות אשד לסינתזה של כהלים אמינו כיראלי מ L-ליזין

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

הכנת יציב Aziridinium Bicyclic יונים, פתיחת הטבעת שלהם לסינתזה של Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles (PPAs) and Related Biomaterials

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). Traditional PAs possess charged amino acids as solubilizing groups (lysine, arginine), which are directly connected to a lipid segment or can contain a linker region made of neutral amino acids. Tuning the peptide sequence of PAs can yield diverse morphologies. Similarly, PPAs possess a hydrophobic segment and neutral amino acids, but also contain polyamine molecules as water solubilizing (hydrophilic) groups. As is the case with PAs, PPAs can also self-assemble into diverse morphologies, including small rods, twisted nano-ribbons, and fused nano-sheets, when dissolved in water. However, the presence of both primary and secondary amines on a single polyamine molecule poses a significant challenge when synthesizing PPAs. In this paper, we show a simple protocol, based on literature precedents, to achieve a facile synthesis of PPAs using solid phase peptide synthesis (SPPS). This protocol can be extended to the synthesis of PAs and other similar systems. We also illustrate the steps that are needed for cleavage from the resin, identification, and purification.

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials

The synthesis of polyamine-based peptide amphiphiles (PPAs) is a significant challenge due to the presence of multiple amine nitrogens, which requires judicious use of protecting groups to mask these reactive functionalities. In this paper, we describe a facile method for the preparation of these new class of self-assembling molecules.

פרוטוקול נתיישב לסינתזה של הרכבה עצמית מבוסס פוליאמין פפטיד חומרים פעילי שטח (PPAs), Biomaterials קשורים

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). ...

Synthesis and Structure Determination of &#181;-Conotoxin PIIIA Isomers with Different Disulfide Connectivities

Peptides with a high number of cysteines are usually influenced regarding the three-dimensional structure by their disulfide connectivity. It is thus highly important to avoid undesired disulfide bond formation during peptide synthesis, because it may result in a completely different peptide structure, and consequently altered bioactivity. However, the correct formation of multiple disulfide bonds in a peptide is difficult to obtain by using standard self-folding methods such as conventional buffer oxidation protocols, because several disulfide connectivities can be formed. This protocol represents an advanced strategy required for the targeted synthesis of multiple disulfide-bridged peptides which cannot be synthesized via buffer oxidation in high quality and quantity. The study demonstrates the application of a distinct protecting group strategy for the synthesis of all possible 3-disulfide-bonded peptide isomers of &#181;-conotoxin PIIIA in a targeted way. The peptides are prepared by Fmoc-based solid phase peptide synthesis using a protecting group strategy for defined disulfide bond formation. The respective pairs of cysteines are protected with trityl (Trt), acetamidomethyl (Acm), and tert-butyl (tBu) protecting groups to make sure that during every oxidation step only the required cysteines are deprotected and linked. In addition to the targeted synthesis, a combination of several analytical methods is used to clarify the correct folding and generation of the desired peptide structures. The comparison of the different 3-disulfide-bonded isomers indicates the importance of accurate determination and knowledge of the disulfide connectivity for the calculation of the three-dimensional structure and for interpretation of the biological activity of the peptide isomers. The analytical characterization includes the exact disulfide bond elucidation via tandem mass spectrometry (MS/MS) analysis which is performed with partially reduced and alkylated derivatives of the intact peptide isomer produced by an adapted protocol. Furthermore, the peptide structures are determined using 2D nuclear magnetic resonance (NMR) experiments and the knowledge obtained from MS/MS analysis.

Cysteine-rich peptides fold into distinct three-dimensional structures depending on their disulfide connectivity. Targeted synthesis of individual disulfide isomers is required when buffer oxidation does not lead to the desired disulfide connectivity. The protocol deals with the selective synthesis of 3-disulfide-bonded peptides and their structural analysis using NMR and MS/MS studies.

סינתזה וקביעת מבנה ממוצע-Conotoxin Isomers PIIIA עם Connectivities דיסולפידי שונים

Peptides with a high number of cysteines are usually influenced regarding the three-dimensional structure by their disulfide connectivity. It is thus ...

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and functionalize polymer chains with compounds that are able to improve biocompatibility, mechanical properties, or cell viability allows the design of novel materials to meet new challenges in the biomedical field. With the polymer functionalization strategies, click chemistry is a powerful tool to improve cell-compatibility and drug delivery properties of polymeric devices. Similarly, the fundamental need of biomedicine to use sterile tools to avoid potential adverse-side effects, such as toxicity or contamination of the biological environment, gives rise to increasing interest in the microwave-assisted strategy.
The combination of click chemistry and the microwave-assisted method is suitable to produce biocompatible hydrogels with desired functionalities and improved performances in biomedical applications. This work aims to synthesize RGD-functionalized hydrogels. RGD (arginylglycylaspartic acid) is a tripeptide that can mimic cell adhesion proteins and bind to cell-surface receptors, creating a hospitable microenvironment for cells within the 3D polymeric network of the hydrogels. RGD functionalization occurs through Huisgen 1,3-dipolar cycloaddition. Some PAA carboxyl groups are modified with an alkyne moiety, whereas RGD is functionalized with azido acid as the terminal residue of the peptide sequence. Finally, both products are used in a copper catalyzed click reaction to permanently link the peptide to PAA. This modified polymer is used with carbomer, agarose and polyethylene glycol (PEG) to synthesize a hydrogel matrix. The 3D structure is formed due to an esterification reaction involving carboxyl groups from PAA and carbomer and hydroxyl groups from agarose and PEG through microwave-assisted polycondensation. The efficiency of the gelation mechanism ensures a high degree of RGD functionalization. In addition, the procedure to load therapeutic compounds or biological tools within this functionalized network is very simple and reproducible.

We present a protocol for the synthesis of RGD-functionalized hydrogels as devices for cell and drug delivery. The procedure involves copper catalyzed alkyne-azide cycloaddition (CuAAC) between alkyne-modified polyacrylic acid (PAA) and a RGD-azide derivative. The hydrogels are formed using microwave-assisted polycondensation and their physicochemical properties are investigated.

הסינתזה של RGD פונקציונלית הידרוג ככלי יישומים טיפוליים

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and ...

Bioengineering

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very difficult and laborious to make aziridines in optically pure forms on a large scale to apply asymmetric synthesis of aza compounds. Fortunately, we successfully achieved both enantiomers (2R)- and (2S)-aziridine-2-carboxylates with the electron-donating &#945;-methylbenzyl group at the ring nitrogen as non-activated aziridines. These starting aziridines have two distinct functional groups-highly reactive three-membered ring and versatile carboxylate. They are applicable in ring-opening or ring-transformation with aziridine and in functional group transformation to others from carboxylate. Both of these enantiomers were utilized in the preparation of biologically important amino acyclic and/or aza-heterocyclic compounds in an asymmetric manner. Specifically, this report describes the first expedient asymmetric synthesis of both enantiomers of 5, 6-dihydrouracil-type marine natural products biemamide B and D as potential TGF-&#946; inhibitors. This synthesis consisted of regio- and the stereoselective ring-opening reaction of aziridine-2-carboxylate and subsequent formation of 4-aminoteterahydropyrimidine-2,4-dione. One more example in this protocol dealt a highly stereoselective Mukaiyama reaction of aziridine-2-carboxylate and silyl enol ether, following intramolecular aziridine ring-opening to provide easy and facile access to (-)-epiallo-isomuscarine.

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

In this study, we prepare both enantiomers of aziridine-2-carboxylate, which are used in the asymmetric synthesis of alkaloids, including biemamide B and D, and (-)-epiallo-isomuscarine.

הכנת אזירידינים לא פעילים של אננטיופור וסינתזה של ביאמאמיד B, D ואפיאלו-איזומוסקרין

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very ...

Preparation of 1&deg; Amines: Azide Synthesis

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum hydride, or by catalytic hydrogenation to primary amines. The driving force for such reactions is the elimination of nitrogen gas.
Azide synthesis also works with other electrophiles like epoxides to produce amino alcohols through stereoselective ring-opening reactions. Alkyl azides have an explosive nature and must be carefully handled.

Preparation of 1&amp;deg; Amines: Azide Synthesis

הכנת 1° אמינים: סינתזת אזיד

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide ...