Resolution of a CPzI precursor, synthesis and biological evaluation of (+) and (-)-N-Boc-CPzI: a further validation of the relationship between chemical solvolytic stability and cytotoxicity

P G Baraldi; B Cacciari; R Romagnoli; G Spalluto; C W Boyce; D L Boger

doi:10.1016/s0960-894x(99)00533-8

Resolution of a CPzI precursor, synthesis and biological evaluation of (+) and (-)-N-Boc-CPzI: a further validation of the relationship between chemical solvolytic stability and cytotoxicity

Bioorg Med Chem Lett. 1999 Nov 1;9(21):3087-92. doi: 10.1016/s0960-894x(99)00533-8.

Authors

P G Baraldi¹, B Cacciari, R Romagnoli, G Spalluto, C W Boyce, D L Boger

Affiliation

¹ Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. [email protected]

PMID: 10560730
DOI: 10.1016/s0960-894x(99)00533-8

Abstract

The chemical resolution, using N-tosyl-L-proline as a chiral auxiliary, of a racemate of the pyrazole analog (+/-)-N-Boc-CPzI of the left hand segment (CPI) of the antitumor agent CC-1065, and the cytotoxic evaluation of both enantiomers are described. The reported results further validate the direct relationship between chemical solvolytic stability of the cyclopropane ring and cytotoxicity proposed by Boger and coworkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibiotics, Antineoplastic / chemistry*
Antineoplastic Agents, Alkylating / chemistry*
Duocarmycins
Indoles*
Leucomycins / chemistry*
Leukemia L1210
Mice
Molecular Structure
Proline / analogs & derivatives
Pyrazoles / isolation & purification*
Pyrazoles / pharmacology
Stereoisomerism
Streptomyces / chemistry
Tumor Cells, Cultured

Substances

Antibiotics, Antineoplastic
Antineoplastic Agents, Alkylating
Duocarmycins
Indoles
Leucomycins
N-Boc-CPzI
Pyrazoles
CC 1065
Proline