Total synthesis of a cytotoxic acetogenin,pyranicin

[structure: see text] The first total synthesis of a new cytotoxic acetogenin, pyranicin (1), is described. SmI(2)-induced reductive cyclization of beta-alkoxy acrylate 4 proceeded stereoselectively to give 16,20-syn-19,20-trans-THP derivative 14, which was efficiently transformed into the 19,20-cis-THP derivative 18 through Mitsunobu lactonization. Wittig reaction of the phosphonium salt 2 obtained therefrom with butenolide 3 at -78 degrees C followed by reduction and deprotection afforded 1 in good overall yield.     

Simple and efficient synthesis of highly functionalized cyclohexanes; formal total synthesis of ovalicin and fumagillin

Two chiral cyclohexanes 4 and 6, which are key intermediates for the total synthesis of ovalicin 1 and fumagillin 2, respectively, were synthesized from (2R,3S) 1,2-epoxy-4-penten-3-ol. The key steps involve an efficient construction of divinylalcohol 7 using methallyl Grignard reagent 9c, and an intramolecular olefin metathesis of 7.     

Large-Scale Preparation of N,N'-Diacetylchitobiose by Enzymic Degradation of Chitin and its Chemical Modifications

Abstract

Hundred gram quantities of peracetylated chitobiose were prepared by degradation of colloidal chitin with commercially available chitinase (EC 3.2.1.14) from Streptomyces griseus and subsequent acetylation, the product being readily convertible into N, N'-diacetylchitobiose by conventional de-O-acetylation. These chitobiose derivatives were subjected to further chemical modifications to give novel disaccharide derivatives composed of a pair of 2-acetamido-2-deoxy-D-allopyranose moieties that are potential intermediates for the synthesis of an enzyme inhibitor.     

Asymmetric Total Synthesis of Heronamides A–C: Stereochemical Confirmation and Impact of Long‐Range Stereochemical Communication on the Biological Activity

Heronamides are biosynthetically related metabolites isolated from marine‐derived actinomycetes. Heronamide C shows potent antifungal activity by targeting membrane phospholipids possessing saturated hydrocarbon chains with as‐yet‐unrevealed modes of action. In spite of their curious hypothesized biosynthesis and fascinating biological activities, there have been conflicts in regard to the reported stereochemistries of heronamides. Here, we describe the asymmetric total synthesis of the originally proposed and revised structures of heronamide C, which unambiguously confirmed the chemical structure of this molecule. We also demonstrated nonenzymatic synthesis of heronamides A and B from heronamide C, which not only proved the postulated biosynthesis, but also confirmed the correct structures of heronamides A and B. Investigation of the structure–activity relationship of synthetic and natural heronamides revealed the importance of both long‐range stereochemical communication and the 20‐membered macrolactam ring for the biological activity of these compounds.     

Total synthesis of the proposed structure for pyragonicin

[structure: see text] The total synthesis of acetogenin 1 reported for pyragonicin and its 10-epimer 32 is described. The common THP ring system was stereoselectively constructed through a SmI(2)-induced reductive cyclization of beta-alkoxy acrylate 5 followed by Mitsunobu inversion, and each chiral center at C-10 was created by Brown's asymmetric allylation. Compound 1 had spectroscopic data consistent with that of natural pyragonicin, but a different optical rotation.