737782-85-3

Upstream product

• 203126-90-3 (3S,4S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne 
• 639460-28-9 (4R,5R)-5-((R)-2-{(1R,3aR,7aR)-4-[1-Bromo-meth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-propyl)-4-methyl-3-methylene-dihydro-furan-2-one 
• 33935-64-7 methyl 2-(bromomethyl)-2-butenoate 
• 639460-36-9 2,2-Dimethyl-propionic acid (3R,4R,6R)-6-{(1R,3aR,7aR)-4-[1-bromo-meth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-4-hydroxy-3-methyl-2-methylene-heptyl ester 
• 639460-32-5 2,2-Dimethyl-propionic acid (3R,6R)-6-{(1R,3aR,7aR)-4-[1-bromo-meth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-3-methyl-2-methylene-4-oxo-heptyl ester 
• 639460-47-2 (3R,4R,6R)-6-{(1R,3aR,7aR)-4-[1-Bromo-meth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-3-methyl-2-methylene-heptane-1,4-diol 
• 173388-41-5 (1R,4E,3aR,7aR)-4-bromomethylene-1-[(1R)-2-formyl-1-methylethyl]-7a-methylperhydroindene 

Relevant academic research and scientific papers

Further synthetic and biological studies on vitamin D hormone antagonists based on C24-alkylation and C2α-functionalization of 25-dehydro-1α- hydroxyvitamin D3-26,23-lactones

An efficient synthesis and the biological evaluation of 80 novel analogs of 25-dehydro-1α-hydroxyvitamin D3-26,23S-lactone 2 (TEI-9647) and its 23R epimer (3) in which the lactone ring was systematically functionalized by introduction of a C1 to C4 primary alkyl group at the C24 position (5 sets of 4 diastereomers), together with their C2α-methyl, 3-hydroxypropyl, and 3-hydroxypropoxy-substituted derivatives were described. The triene structure of the vitamin D3 was constructed using palladium-catalyzed alkenylative cyclization of the A-ring precursor enyne with the CD-ring counterpart bromoolefin having the C24-alkylated lactone moiety on the side chain. The CD-ring precursors having 23,24-cis lactones were prepared by using a chromium-mediated syn-selective allylation-lactonization process, and the 23,24-trans lactone derivatives were derived from these via inversion of the C23 stereochemistry. The biological evaluation revealed that both binding affinity for chick vitamin D hormone receptor and antagonistic activity (inhibition of vitamin D hormone induced HL-60 cell differentiation) were affected by the orientation and chain-length of the primary alkyl group on the lactone ring. Furthermore, the C2α-functionalization of the C24-alkylated vitamin D3 lactones dramatically enhanced their biological activities. The most potent compound to emerge, (23S,24S)-2α-(3-hydroxypropoxy)-24-propyl exhibited almost 1000-fold stronger antagonistic activity (IC50 = 7.4 pM) than 2 (IC50 = 6.3 nM).