lavendamycin

Lavendamycin was first discovered in 1981 by Doyle et al., who isolated it from Streptomyces lavendulae. As the compound failed to crystallize, a direct characterization of the molecular structure with X-ray crystallography was not possible. Careful analysis using NMR, IR, and UV-VIS spectroscopy and mass spectrometry allowed the assignment of the pentacyclic structure consisting of a β-carboline unit and a quinolinequinone unit.{{cn|date=February 2023}}

The attractive biological properties and complex structure of lavendamycin have made it the target of a large number of total syntheses.{{Cite journal|last1=Bringmann|first1=Gerhard|last2=Reichert|first2=Yanina|last3=Kane|first3=Vinayak V.|date=2004|title=The total synthesis of streptonigrin and related antitumor antibiotic natural products|url=https://linkinghub.elsevier.com/retrieve/pii/S0040402004003333|journal=Tetrahedron|language=en|volume=60|issue=16|pages=3539–3574|doi=10.1016/j.tet.2004.02.060}} Within a few years after the structural elucidation by Doyle et al., the research groups of Kende,{{Cite journal|last1=Kende|first1=Andrew S.|last2=Ebetino|first2=Frank H.|date=1984|title=The regiospecific total synthesis of lavendamycin methyl ester|url=https://linkinghub.elsevier.com/retrieve/pii/S0040403901800630|journal=Tetrahedron Letters|language=en|volume=25|issue=9|pages=923–926|doi=10.1016/S0040-4039(01)80063-0}} Hibino,{{Cite journal|last1=Hibino|first1=Satoshi|last2=Okazaki|first2=Miko|last3=Sato|first3=Kohichi|last4=Morita|first4=Itsuko|last5=Ichikawa|first5=Masataka|date=1983|title=Synthetic Approach to the Antitumor Antibiotic Lavendamycin: a Synthesis of Demethallavendamycin Methyl Ester|url=http://www.heterocycles.jp/library/abstract.php?doi=10414|journal=Heterocycles|language=en|volume=20|issue=10|pages=1957|doi=10.3987/R-1983-10-1957|issn=0385-5414|doi-access=free}} Rao,{{Cite journal|last1=Rao|first1=A.V.Rama|last2=Chavan|first2=Subhash P.|last3=Sivadasan|first3=Latha|date=1986|title=Synthesis of lavendamycin|url=https://linkinghub.elsevier.com/retrieve/pii/S0040402001880583|journal=Tetrahedron|language=en|volume=42|issue=18|pages=5065–5071|doi=10.1016/S0040-4020(01)88058-3}} and Boger{{Cite journal|last1=Boger|first1=Dale L.|last2=Duff|first2=Steven R.|last3=Panek|first3=James S.|last4=Yasuda|first4=Masami|date=1985|title=Total synthesis of lavendamycin methyl ester|url=https://pubs.acs.org/doi/abs/10.1021/jo00350a070|journal=The Journal of Organic Chemistry|language=en|volume=50|issue=26|pages=5790–5795|doi=10.1021/jo00350a070|issn=0022-3263}} had already developed total syntheses for the compound independently of one another. The discovery that analogs of lavendamycin are potent inhibitors of HIV reverse transcriptase led to further attempts in the 90s to develop efficient routes to lavendamycin.{{Cite journal|last1=Ciufolini|first1=Marco A.|last2=Bishop|first2=Michael J.|date=1993|title=Studies towards streptonigrinoids: formal synthesis of lavendamycin methyl ester|url=http://xlink.rsc.org/?DOI=c39930001463|journal=Journal of the Chemical Society, Chemical Communications|language=en|issue=18|pages=1463–1464|doi=10.1039/c39930001463|issn=0022-4936}}{{Cite journal|last1=Molina|first1=Pedro|last2=Fresneda|first2=Pilar M.|last3=Cánovas|first3=Mercedes|date=1992|title=Iminophosphorane-mediated synthesis of 1-substituted-β-carbolines: investigative studies on the preparation of alkaloids lavendamycin and eudistomins framework.|url=https://linkinghub.elsevier.com/retrieve/pii/S0040403900788885|journal=Tetrahedron Letters|language=en|volume=33|issue=20|pages=2891–2894|doi=10.1016/S0040-4039(00)78888-5}}{{Cite journal|last1=Molina|first1=Pedro|last2=Murcia|first2=Fernando|last3=Fresneda|first3=Pilar M.|date=1994|title=A straightforward and practical formal synthesis of lavendamycin ethyl ester|url=https://linkinghub.elsevier.com/retrieve/pii/S0040403900762447|journal=Tetrahedron Letters|language=en|volume=35|issue=9|pages=1453–1456|doi=10.1016/S0040-4039(00)76244-7}}{{Cite journal|last1=Rocca|first1=Patrick|last2=Marsais|first2=Francis|last3=Godard|first3=Alain|last4=Quéguiner|first4=Guy|date=1993|title=A new approach to the synthesis of lavendamycin analogues.|url=https://linkinghub.elsevier.com/retrieve/pii/S0040403900604860|journal=Tetrahedron Letters|language=en|volume=34|issue=18|pages=2937–2940|doi=10.1016/S0040-4039(00)60486-0}} However, large numbers of steps, low overall yields (0.5–2%) or poorly available starting materials make these syntheses unattractive for further systematic development of lavendamycin and its analogs. Notably, total syntheses by Behforouz{{Cite journal|last1=Behforouz|first1=Mohammad|last2=Gu|first2=Zhengxiang|last3=Cai|first3=Wen|last4=Horn|first4=Mark A.|last5=Ahmadian|first5=Mohammad|date=1993|title=A highly concise synthesis of lavendamycin methyl ester|url=https://pubs.acs.org/doi/abs/10.1021/jo00077a032|journal=The Journal of Organic Chemistry|language=en|volume=58|issue=25|pages=7089–7091|doi=10.1021/jo00077a032|issn=0022-3263}} and Nissen{{Cite journal|last1=Nissen|first1=Felix|last2=Detert|first2=Heiner|date=2011|title=Total Synthesis of Lavendamycin by a [2+2+2] Cycloaddition|url=https://onlinelibrary.wiley.com/doi/10.1002/ejoc.201100131|journal=European Journal of Organic Chemistry|language=en|volume=2011|issue=15|pages=2845–2853|doi=10.1002/ejoc.201100131}} offer flexible construction of the lavendamycin scaffold at high yields.

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Category:Streptomyces

Category:Beta-Carbolines

Category:Carboxylic acids

Category:Antibiotics