201011-92-9Relevant articles and documents
Amphidinolide J: A cytotoxic macrolide from the marine dinoflagellate Amphidinium sp. determination of the absolute stereochemistry
Kobayashi,Sato,Ishibashi
, p. 2645 - 2646 (1993)
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13-Methyl-substituted des-C,D analogs of (20S)-1α,25-dihydroxy-2-methylene-19-norvitamin D3 (2MD): Synthesis and biological evaluation
Plonska-Ocypa, Katarzyna,Sicinski, Rafal R.,Plum, Lori A.,Grzywacz, Pawel,Frelek, Jadwiga,Clagett-Dame, Margaret,DeLuca, Hector F.
experimental part, p. 1747 - 1763 (2009/08/15)
Analogs of (20S)-1α,25-dihydroxy-2-methylene-19-norvitamin D3 (2, 2MD), substituted at C-13 but lacking both C and D rings, were prepared in convergent syntheses, starting with the chiral ester 14 and the phosphine oxide 29. Two of the synthesized vitamins (11 and 32) were analogs in which the 13-methyl group constituted a substituent of an unsaturated fragment, that is, C(13)-C(17) double bond, whereas in the two other cases (12 and 13), the methyl group belonged to a ternary carbon stereogenic center. The aim of these studies was to further explore extensive modifications in the 'upper' part of the vitamin D skeleton in the hope of finding biologically active analogs of potential therapeutic value. The commercial (R)-(-)-methyl-3-hydroxy-2-methylpropionate (14) was converted in six steps to alcohol 18, the vitamin D side chain fragment. Its subsequent three-step transformation led to aldehyde 20 which was subjected to the Still-Gennari HWE reaction with anion derived from ester 21. The obtained α,β-unsaturated esters 22 and 23 served as convenient starting compounds to the syntheses of the corresponding chiral acyclic aldehydes, β,γ-unsaturated (28) and saturated (39 and 40), required for the final Wittig-Horner coupling with the anion of the phosphine oxide 29. After hydroxyl deprotection, the synthesized vitamin D analogs 11-13 and 32 were purified and biologically tested. Only the (13R,20S)-analog 12 retained substantial, although 30 times lower than 1α,25-(OH)2D3, binding ability to the full-length rat recombinant vitamin D receptor (VDR). This analog was also very effective in differentiation of HL-60 cells, and it exerted significant transcriptional activity (2 times and 15 times less potent, respectively, as compared to the native hormone). The in vivo tests showed that all synthesized vitamin D analogs were devoid of calcemic activity.
The first stereoselective total synthesis of lankanolide. Part 2
Hamada, Tatsuo,Kobayashi, Yukinari
, p. 4347 - 4350 (2007/10/03)
The seco-acid derivative designed by conformation calculation and lactonization experiment of model seco-acids was synthesized, and subjected to macrolactonization to afford the lactone derivative. The lankanolide was synthesized via several steps after the lactonization, and the synthetic lankanolide was confirmed to have the same physical data (NMR, mass, IR and αD) as the lankanolide prepared from lankamycin according to the reported method.
