Macrolactonizations in the Total Synthesis of Natural Products

Recent advances in stereoselective c-glycoside synthesis

Following macrolactonization, a Sonogashira coupling leads efficiently from 1 and 2 to the aglycon of the structurally unique cytotoxic macrolide callipeltoside A, isolated in tiny quantities from the lithistid sponge Callipelta sp. Key steps in the preparation of macrolide precursor 1 include a boron-mediated anti-aldol coupling (A) in tandem with Yamamoto's vinylogous aldol reaction (B). TES=triethylsilyl.

Total Synthesis of the Callipeltoside Aglycon.

page v Abstract Leucascandrolide A (I), a polyoxygenated marine macrolide of a new genus (Scheme I), was isolated in 1996 by Pietra and co-workers from the calcareous sponge Leucascandra caveolata. Despite intensive efforts, subsequent expeditions failed to provide additional quantities of I. The biological profile of I is characterized by strong cytotoxic activity against human cancer cell lines as well as powerful inhibition of Candida albicans. This thesis describes the total synthesis of leucascandrolide A. The synthesis planning, outlined in Scheme I, relies on the use of asymmetric synthetic methods recently developed in our laboratories and was chosen for reasons of flexibility and convergency.Leucascandrolide A (I), a polyoxygenated marine macrolide of a new genus (Scheme I), was isolated in 1996 by Pietra and co-workers from the calcareous sponge Leucascandra caveolata. Despite intensive efforts, subsequent expeditions failed to provide additional quantities of I. The biological profile of I is characterized by strong cytotoxic activity against human cancer cell lines as well as powerful inhibition of Candida albicans. This thesis describes the total synthesis of leucascandrolide A. The synthesis planning, outlined in Scheme I, relies on the use of asymmetric synthetic methods recently developed in our laboratories and was chosen for reasons of flexibility and convergency. Me O O O O OMe O Me Me O N O N O MeO H Me Me SO2Ar O Me O OR2 CO2R Me H O OR1 O O Me Me I II III O N O N O MeO H MeO

Total Synthesis of Leucascandrolide A

Mukaiyama aldol-Prins cyclization cascade reaction: a formal total synthesis of leucascandrolide A.

Synthesis of erythronolide a via a very efficient macrolactonization under usual acylation conditions with the Yamaguchi reagent

Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. III: Synthesis of C27-C36 subunit via completely stereoselective C-glycosylation to the F ring

Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. 8. Synthesis of the lactone part (C1C36) via horner-emmons coupling between C1C15 and C16C36 fragments and Yamaguchi lactonization

Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. IV: Synthesis of the C37-C54 subunit via stereoselective construction of three consecutive J, K, and L rings

(2S, 3S)-2-(4-Methoxybenzyloxy)-3, 4-O-(3-pentylidene)-1, 3, 4-butanetriol (3), a versatile chiral building block for an essential structural unit of complex natural products, was synthesized starting from dimethyl L-(+)-tartrate (5) on both a small scale and a large scale in good yield.

Large Laboratory Scale Synthesis of (2S, 3S)-2-(4-Methoxybenzyloxy)-3,4-O-(3-pentylidene)-1,3,4-butantriol, a Versatile Chiral Building Block in Natural Product Synthesis

Y. Sakurai

Papers

Synthesis of erythronolide a via a very efficient macrolactonization under usual acylation conditions with the Yamaguchi reagent

Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. III: Synthesis of C27-C36 subunit via completely stereoselective C-glycosylation to the F ring

Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. 8. Synthesis of the lactone part (C1C36) via horner-emmons coupling between C1C15 and C16C36 fragments and Yamaguchi lactonization

Synthetic studies of halichondrin B, an antitumor polyether macrolide isolated from a marine sponge. IV: Synthesis of the C37-C54 subunit via stereoselective construction of three consecutive J, K, and L rings

Large Laboratory Scale Synthesis of (2S, 3S)-2-(4-Methoxybenzyloxy)-3,4-O-(3-pentylidene)-1,3,4-butantriol, a Versatile Chiral Building Block in Natural Product Synthesis