Synthetic studies on the marine natural product halichondrins

Abstract

In connection with the de elopment of a practical synthesis of the right half, and its analog E7389, of halichondrin B, an efficient and scalable synthesis of the two major building blocks is reported. In addition, a new synthesis of the C20–C26 segment via a regiospecific and stereoselecti e SN2' process is presented. A sulfonamide class of ligands is shown to be effective for asymmetric Ni/Cr-mediated reactions under both stoichiometric and catalytic conditions, and the X-ray structure reveals this class of ligands to be tridentate. On the basis of three X-ray structures, a possible mechanism is suggested for this process. Stable and crystalline Cr(III)/sulfonamide complexes are shown to be effective for catalytic Cr-mediated coupling reactions of allyl, alkenyl, and alkyl halides with aldehydes, and some examples for application of the stoichiometric and catalytic asymmetric processes are presented.

Sponge-Associated Microorganisms: Evolution, Ecology, and Biotechnological Potential

“…Nevertheless, halichondrin B may yet prove to be a success story, with a synthetic analog, E7389, in phase I clinical trials as an anticancer compound (370). This simplified version of halichondrin B is more amenable to chemical synthesis but retains the biological activities of the original compound (60).…”

Total Synthesis of Desmethyl Macrolide Antibiotics

“…47 Moreover, Kishi had demonstrated that the intermolecular NHK reaction was extraordinarily effective in the coupling of complex fragments in natural product total synthesis. 48 Thus, we reasoned that applying the 'more popular modes' of these powerful reactions would help realize the total synthesis of 6. This constituted our second deviation from previous routes.…”

Selected hybrid natural products as tubulin modulators

“…It was converted to the C30a modified derivative (structure not shown) in 14 synthetic transformations with an overall 23 steps from a commercial starting material with an overall yield of 1.3% [54]. Later, Kishi's team developed a practical synthesis of fragment 6.1 from the commercial available starting material D-(þ)-Glucurono-6,3-lactone [55]. In the second generation synthesis of fragment 6.1, the C30 PhSO 2 CH 2 group was introduced stereoselectively (>100:1) via hydrogenation using the Crabtree catalyst.…”