311342-01-5Relevant academic research and scientific papers
Rapid entry into the cryptophycin core via an acyl-beta-lactam macrolactonization: total synthesis of cryptophycin-24.
Eggen,Nair,Georg
, p. 1813 - 1815 (2001)
[see structure]. An efficient, concise approach to the macrolide core of the cryptophycins, potent antimitotic agents, has been achieved. The reaction sequence features a novel macrolactonization utilizing a reactive acyl-beta-lactam intermediate that inc
Frontiers and opportunities in chemoenzymatic synthesis
Mortison, Jonathan D.,Sherman, David H.
scheme or table, p. 7041 - 7051 (2010/12/20)
Natural product biosynthetic pathways have evolved enzymes with myriad activities that represent an expansive array of chemical transformations for constructing secondary metabolites. Recently, harnessing the biosynthetic potential of these enzymes through chemoenzymatic synthesis has provided a powerful tool that often rivals the most sophisticated methodologies in modern synthetic chemistry and provides new opportunities for accessing chemical diversity. Herein, we describe our research efforts with enzymes from a broad collection of biosynthetic systems, highlighting recent progress in this exciting field.
Synthesis of Cryptophycins via an N-Acyl-β-lactam Macrolactonization
Vidya, Ramdas,Eggen, MariJean,Nair, Sajiv K.,Georg, Gunda I.,Himes, Richard H.
, p. 9687 - 9693 (2007/10/03)
An efficient and concise approach to the synthesis of the macrolide core of the cryptophycins has been developed. A novel macrolactonization utilizing a reactive acyl-β-lactam intermediate incorporates the β-amino acid moiety within the 16-membered macrol
Total synthesis of cryptophycin-24 (arenastatin A) amenable to structural modifications in the C16 side chain
Eggen,Mossman,Buck,Nair,Bhat,Ali,Reiff,Boge,Georg
, p. 7792 - 7799 (2007/10/03)
Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E,7E)-5-[(tert-butyldimethylsilyl)-oxy]-6-methyl-8-phenyl-2,7-octadie noate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-α-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2,7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).
