Paulo R. R. Meira

Synthesis of C13C22 fragment of the marine sponge polyketide callystatin A

We wish to report here our initial efforts towards the total synthesis of callystatin A, describing the synthesis of the C13C22 fragment. This asymmetric approach uses an efficient syn-aldol reaction, and a diastereoselective epoxidation of an allylic alcohol with m-CPBA followed by epoxide opening with Me2CuLi.

Synthesis of C1C11 fragment of callystatin A

Abstract We wish to describe here our continuing efforts towards the total synthesis of the marine sponge polyketide callystatin A, describing the synthesis of the C1C11 fragment.

CorrigendumCorrigendum to “Synthesis of C13–C22 fragment of the marine sponge polyketide callystatin A”: [Tetrahedron Lett. 43 (2002) 185–187]

Selective DIBALH-mediated acetal cleavage in 13 gave the desired p-methoxybenzyl ether alcohol 16 in 94% yield with complete regioselectivity (Scheme 5). Dess–Martin periodinane oxidation of 16 under standard conditions followed by PMB removal, Wittig type coupling with carboethoxyethylidene–triphenylphosphorane and reprotection of the secondary alcohol function gave , -unsaturated ester 3 (E:Z>95:5) in 90% overall yield for the four-step sequence, corresponding to the C13–C22 fragment of callystatin A. We have observed that the PMB-protected aldehyde derived from 16 is unreactive under the Wittig type coupling. Using this PMB-aldehyde we have observed starting material and elimination of the p-methoxybenzyl alcohol to give the corresponding , -unsaturated aldehyde 17, even using refluxing CH2Cl2. The 14-step sequence from 6 to 3 proceeded in an overall yield of 42% and is amenable to a multigram scale-up.

Recent results toward the stereoselective synthesis of biologically active natural products

This paper describes the convergent and stereocontrolled asymmetric total synthesis of (+)-crocacins C and D, potent inhibitors of animal cell cultures and several yeasts and fungi, and (-)-callystatin A, a potent antitumor polyketide.