737004-07-8

Upstream product

• 808752-79-6 (-)-(3'R,5'S,8'R)-N-[1-(8'-allyloxy-7'-oxa-[3.3.0]-bicyclooct-1'-ene-3'-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-benzamide 
• 808752-62-7 (-)-(3R,5S,8R)-8-allyloxy-2-trimethylsilyl-7-oxa-[3.3.0]-bicyclooct-1-ene-3-ol 
• 808752-59-2 (5S,8R)-8-allyloxy-2-trimethylsilyl-7-oxa-[3.3.0]-bicyclooct-1-ene-3-one 
• 808752-66-1 (-)-(3R,5S,8R)-acetic acid 8-allyloxy-7-oxa-[3.3.0]-bicyclooct-1-ene-3-yl ester 
• 808752-64-9 (-)-(3R,5S,8R)-8-allyloxy-7-oxa-[3.3.0]-bicyclooct-1-ene-3-ol 
• 58479-61-1 tert-butylchlorodiphenylsilane 

Downstream Products

• 737004-23-8 (-)-(1R,4S)-N-{1-[4-(tert-butyl-diphenyl-silanyloxymethyl)-3-hydroxymethyl-cyclopent-2-en-1-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-benzamide 

Relevant academic research and scientific papers

NUCLEOSIDE ANALOGUES WITH APOPTOSIS-INDUCING CHARACTERISTICS FOR TREATING DISEASES CAUSED BY RAPIDLY PROLIFERATING CELLS

The invention relates to medicaments and compounds for treating diseases caused by rapidly proliferating cells such as tumour cells, in particular blast cells in children with acute leukaemia. The invention also relates to the production of corresponding medicaments and compounds.

Transition-metal-mediated synthesis of novel carbocyclic nucleoside analogues with antitumoral activity

A diversity-oriented, enantioselective synthesis of new (monoprotected) carbocyclic nucleoside analogues (CNAs) with the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethylcyclopent-2-en-l -yl scaffold was developed. As a key intermediate, racemic (5SR,8RS)-8-allyloxy-2-trimethylsilyl- 7-oxa-bicyclo[3.3.0]-oct-1-en-3-one was prepared from 1,1-diallyloxy-3- trimethylsilyl-2-propyne in a cobalt-mediated Pauson-Khand reaction. The enantiomerically pure material was obtained through efficient kinetic resolution (selectivity factor s ≥ 40 at -78°C) by means of an oxazaborolidine- catalyzed borane reduction (CBS reduction) with catecholborane. The absolute configuration of the resolved products was determined by CD spectroscopy, Mosher ester analysis, and chemical correlation. Subsequent steps involve diastereoselective ketone reduction and fully regio- and diastereoselective introduction of the nucleobase through Pd°-catalyzed allylic substitution. The generality of the method was demonstrated by preparation of CNAs in both enantiomeric series with all five natural nucleobases, as well as 5-bromouracil, 5-fluorouracil, and 6-chloropurine. Screening of the various compounds in a cytotoxicity assay with BJAB and ALL tumor cell lines revealed that some of the compounds possess pronounced antitumoral properties (LD50 values down to 9 μM, as determined by lactate dehydrogenase release after 48 h). By measuring DNA fragmentation, it could be shown that the activity results from induction of apoptosis.