21090-92-6Relevant articles and documents
Total syntheses of the non-peptide bradykinin B1 receptor antagonist velutinol a and its analogs, seco-pregnanes with a cage-like moiety
Tamiya, Minoru,Isaka, Nobuhisa,Kitazawa, Takaaki,Hasegawa, Atsushi,Ishizawa, Kazuya,Ikeda, Mayu,Kawada, Saki,Ishiguro, Masaji
, p. 1474 - 1494 (2019/09/30)
We describe here the syntheses of velutinol A (1) and the structurally similar compounds 24 sharing a highly oxygenated seco-pregnane cage-like structure. The synthesis of velutinol A (1, 15,16-seco-pregnane) features the highly regioselective construction of |14 silyl enol ether from 15-keto-21,22-diol, followed by stereoselective introduction of a sterically hindered β-hydroxy group at the C14 position by Rubottom oxidation. Prolonged reaction time and the use of an excess amount of mCPBA at this step allowed double Rubottom oxidation, enabling us to introduce the requisite hydroxy groups at the C14 and C16 positions in one pot. Subsequent oxidative cleavage of the C1516 bond, deprotection, and intramolecular acetalization allowed the concise total synthesis of velutinol A (1). Utilization of α,α-dihydroxy-ketone, the double Rubottom oxidation product, for formation of the ether F-ring by 5-exo-cyclization, and subsequent C1421 oxidative cleavage, effectively achieved the synthesis of pentalinonside-aglycon (2). Construction of the 14,15-seco-structures of two other analogs, argeloside aglycon (3) and illustrol (4), was achieved by BaeyerVilliger oxidation of 15(21)-keto derivatives. Introduction of the 20-oxo group potentially embedded in argeloside aglycon was accomplished by Wacker oxidation of |20, which was constructed by GriecoNishizawa syn-β-elimination of the C21-primary alcohol obtained by reduction of the BaeyerVilliger product. Intra-molecular double acetalization of the 15,16-dihydroxy-14,20-oxo derivative to form the cage-like structure of the DEF-rings required a moderately weak acid. This step was the key to accessing argeloside aglycon (3), as otherwise the easily aromatized β,γ-dihydroxyketone moiety was transformed to furan. Sharpless asymmetric dihydroxylation of |20 to set the C20 stereocenter, followed by intramolecular double acetalization, achieved the stereoselective synthesis of illustrol With all synthesized compounds, structural requirements of steroidal bradykinine B1 receptor antagonist would be revealed.
Synthesis and Diels-Alder reactions of dieno-pyranosides
Giuliano, Robert M.,Buzby, John H.
, p. C1 - C4 (2007/10/02)
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