Total synthesis of epothilone A

Hindupur, Rama Mohan; Panicker, Bijoy; Valluri, Muralikrishna; Avery, Mitchell A.

doi:10.1016/s0040-4039(01)01585-4

Cited by 39 publications

(16 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The southern building block of the macrolactone was prepared in three synthetic steps (Scheme 3). The synthesis began with silyl etherification [18] of the known chiral epoxy alcohol 13 (93 %, e.r. > 99:1), which is accessible through kinetic resolution of 3-buten-2-ol by using Sharpless epoxidation.…”

mentioning

confidence: 99%

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

2014

View full text Add to dashboard Cite

Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug-resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18-membered macrolactone is reported herein. The key reactions include ring-closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium-sized fragments, thus leading to a flexible yet convergent synthetic route. COMMUNICATION Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)Hideki Miyatake-Ondozabal, Elias Kaufmann and Karl Gademann* Dedication ((optional)) Abstract: Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have an excellent bactericidal activity against multi-drug resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has ever been reported to date. Herein, we report the enantioselective synthesis of the central 18-membered macrolactone. The noteworthy reactions include ringclosing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis comprises of three medium sized fragments leading to a flexible yet convergent synthetic route.

show abstract

mentioning

confidence: 99%

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

2014

View full text Add to dashboard Cite

show abstract

“…[32][33][34][35] Our overall retrosynthetic approach to this class of molecules is shown in Scheme 1. [33] We envisioned using a convergent, two-step sequence involving a double-diastereoselective aldol condensation between the aldehyde 5 and the keto acid 6, followed by Yamaguchi macrolactonization to form the target epothilone framework.…”

Section: Recent Total Syntheses Of the Epothilonesmentioning

confidence: 99%

Recent Developments in the Syntheses of the Epothilones and Related Analogues

2006

View full text Add to dashboard Cite

The macrocyclic class of antitumor compounds known as the epothilones has generated considerable interest since its discovery in 1993. Numerous total syntheses of this class of molecules have been published and countless structural analogues have been developed and tested for their abilities to promote tubulin polymerization. Several of these compounds are presently in clinical trials.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

show abstract

“…This compound has various applications stemming from the fact that it belongs to the optically active compounds. (2S,3R)-1,2-Epoxybutane-3-ol is used in the synthesis of drugs under the name Epothilone B [16] and A [17]. Epothilone B is labelled as EPO906 and is currently in clinical studies.…”

Section: Introductionmentioning

confidence: 99%