Crystallographic determination of stereochemistry of biologically active 2'',3''-dibromo-7-epi-10-deacetylcephalomannine.
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.
Jiang
Yi
Y
Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China.
Lin
Hai-Xia
HX
Chen
Jian-Min
JM
Chen
Min-Qin
MQ
D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D017239:Paclitaxel / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D043823:Taxoids; C056348:cephalomannine; D017239:Paclitaxel