ABSTRACT
[reaction: see text] The most recently described member of the cacospongionolide class of marine natural products has been assembled using a diastereochemically divergent total synthesis strategy that independently establishes the complete stereochemistry of cacospongionolide F and provides a new entry toward expansion of this phospholipase A(2) inhibitor chemotype.
Subject(s)
Lactones/chemistry , Lactones/chemical synthesis , Terpenes/chemistry , Terpenes/chemical synthesis , Animals , Models, Molecular , Molecular Conformation , Molecular Structure , Phospholipases A/antagonists & inhibitors , Phospholipases A/metabolism , Porifera/chemistry , Sesterterpenes , StereoisomerismABSTRACT
[reaction: see text] Via an X-ray analysis, the sulfonamide bearing R(1) = i-Pr, R(2) = Me, and R(3) = Me is shown to be a tridentate ligand to a Cr(III) salt. This class of ligands, represented by R(1) = t-Bu, R(2) = 2-naphthyl, and R(3) = Me, is effective to achieve an asymmetric Ni/Cr-mediated coupling reaction and, with the C14-C38 segment of halichondrins, its synthetic potential has been demonstrated. A possible mechanism is suggested for the process.
Subject(s)
Chromium/chemistry , Ethers, Cyclic/chemistry , Ethers, Cyclic/chemical synthesis , Nickel/chemistry , Catalysis , Ligands , Macrolides , Molecular Conformation , Molecular Structure , StereoisomerismABSTRACT
[reaction: see text] The stable, crystalline Cr(III)/sulfonamide complex 1a is shown to be an effective catalyst for the Ni/Cr-mediated coupling reaction. A possible mechanism is suggested for the process. 1a is also effective for other Cr-mediated coupling reactions. With this catalyst, a concise and efficient synthesis of the C14-C26 segment of halichondrins has been developed.
