Pentacyclic Furanosteroids: The Synthesis of Potential Kinase Inhibitors Related to Viridin and Wortmannolone

• Published in: Journal of organic chemistry Vol. 74; no. 15; pp. 5429 - 5439
• Main Authors: Lang, Yunhui, Souza, Fabio E. S, Xu, Xinshe, Taylor, Nicholas J, Assoud, Abdeljalil, Rodrigo, Russell
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.08.2009; Amer Chemical Soc
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Androstadienes - chemical synthesis; Androstadienes - chemistry; Androstenes - chemical synthesis; Androstenes - chemistry; Bacteriocins - chemical synthesis; Bacteriocins - chemistry; Benzoquinones - chemistry; Chemistry; Chemistry, Organic; Cyclization; Exact sciences and technology; Molecular Structure; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Science & Technology; Stereoisomerism; Steroids; CHEMISTRY; RING-SYSTEM; DIELS-ALDER REACTIONS; PHOSPHOINOSITIDE 3-KINASE; CYCLOADDITIONS; ALKALOIDS; Pentacyclic compound; Intramolecular reaction; Steroid; Regioselectivity; Molecular structure; Enzyme; Transferases; Quinone; Benzoquinone derivatives; Enzyme inhibitor; Diels Alder addition; Organic silane; Natural compound; Stereochemistry; Tricyclic compound; Cyclization; Kinase; Benzenic compound; Nitrile oxide; Chemical synthesis; Ethylenic compound
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo900922q

A regiocontrolled intermolecular Diels−Alder reaction of an o-benzoquinone followed by an intramolecular nitrile oxide cyclization is employed to prepare the BCD fragment of viridin. The AE segment is attached to it by means of an intramolecular Diels−Alder reaction of an o-benzoquinone monoketal generated in situ from tricycle 15 and 5-trimethylsilyl-2E,4E-pentadienol 20. The silyl substituent at C-1 of the pentacyclic product directs the dihydroxylation of the C2−C3 double bond to its β-face. Various transformations of the 1α-trimethylsilyl-2β,3β-dihydroxy pentacycle into several others with oxygen substituents in ring A are described. One of these products 40 possesses the same structure and relative stereochemistry in rings A, B, and E as that of the natural product wortmannolone 3.