Crystallographic determination of stereochemistry of biologically active 2″,3″-dibromo-7-epi-10-deacetylcephalomannine

Bioorganic & Medicinal Chemistry Letters
2005.0

Abstract

The stereochemistry at C2'' and C3'' of two diastereomers of 2'',3''-dibromo-7-epi-10-deacetylcephalomannine (6 and 7), which were synthesized by reacting 7-epi-10-deacetylcephalomannine (5) with bromine, were assigned unambiguously based on crystallographic studies of 6. The X-ray crystallographic analysis shows that 6 adopts an absolute configuration of (2''S,3''R), and 7 can be assigned as (2''R,3''S) configuration. The side-chain conformation of 6 was revealed to be different with the known hydrophobic collapse and the apolar conformations, as found in solid state and in solution. However, most side-chain torsion angles of 6 were found to be very similar to those of tubulin-bound T-shaped conformation (T-Taxol). Both 6 and 7 showed strong in vitro paclitaxel-like activity.

Knowledge Graph

Similar Paper

Crystallographic determination of stereochemistry of biologically active 2″,3″-dibromo-7-epi-10-deacetylcephalomannine
Bioorganic & Medicinal Chemistry Letters 2005.0
Synthesis and Separation of Potential Anticancer Active Dihalocephalomannine Diastereomers from Extracts of <i>Taxus </i><i>y</i><i>unnanensis</i>
Journal of Natural Products 1998.0
Synthesis and NMR-Driven Conformational Analysis of Taxol Analogues Conformationally Constrained on the C13 Side Chain
Journal of Medicinal Chemistry 2001.0
Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation
Bioorganic &amp; Medicinal Chemistry Letters 2009.0
The structure of manumycin. III. Absolute configuration and conformational studies.
The Journal of Antibiotics 1987.0
Evaluation of the Tubulin-Bound Paclitaxel Conformation:  Synthesis, Biology, and SAR Studies of C-4 to C-3‘ Bridged Paclitaxel Analogues
Journal of Medicinal Chemistry 2007.0
Crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-[(3-cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone
Journal of Medicinal Chemistry 1993.0
Biologically active taxol analogs with deleted A-ring side chain substituents and variable C-2' configurations
Journal of Medicinal Chemistry 1991.0
Potent Antitumor Activities and Structure Basis of the Chiral β-Lactam Bridged Analogue of Combretastatin A-4 Binding to Tubulin
Journal of Medicinal Chemistry 2016.0
Total Synthesis and Anti-Tubulin Activity of Epi-C3 Analogues of Cryptophycin-24
Journal of Medicinal Chemistry 2004.0