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.
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.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. pgb@ifeuniv.unife.it
Cacciari
B
B
Romagnoli
R
R
Spalluto
G
G
Boyce
C W
CW
Boger
D L
DL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins / Q000737:chemistry*; D007939:Leukemia L1210; D051379:Mice; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives; D011720:Pyrazoles / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; C104542:N-Boc-CPzI; D011720:Pyrazoles; C018782:CC 1065; D011392:Proline