Diosphenol-Based Approach to the A-Ring Functionalization of Advanced Taxol Precursors

• Published in: Journal of organic chemistry Vol. 71; no. 19; pp. 7329 - 7336
• Main Authors: Kreilein, Matthew M, Hofferberth, John E, Hart, Amy C, Paquette, Leo A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.09.2006; Amer Chemical Soc
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Chemistry, Organic; Exact sciences and technology; Molecular Structure; Organic chemistry; Paclitaxel - chemical synthesis; Paclitaxel - chemistry; Phenols - chemistry; Physical Sciences; Preparations and properties; Prodrugs - chemical synthesis; Prodrugs - chemistry; Science & Technology; Stereoisomerism; Terpenoids; OXIDATION; KETONES; METHYL(TRIFLUOROMETHYL)DIOXIRANE; 1ST TOTAL-SYNTHESIS; ALPHA-DIKETONES; ENANTIOSELECTIVE TOTAL-SYNTHESIS; ASYMMETRIC TOTAL-SYNTHESIS; STEREOCONTROLLED SYNTHESIS; PINENE PATH; C-RING; Terpenoid; Diol; Ether; Regioselectivity; Bromination; Silylation; Enol; Methanolysis; Sodium Tetrahydroborates; Allylation; Chemical reduction; Terpene; Functionalization; Steric effect; Taxane derivatives; Diterpene; Epoxidation; Oxidation; Methylation; Oxygenation; Acid medium; Protection; Acylation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo061115+

Several different approaches to the A-ring functionalization of an advanced, highly functionalized diosphenol precursor to Taxol are described. The first phase of the undertaking consists of an assessment of those reagents conducive to reaction at the enolic oxygen (silylation, methylation, allylation, and acylation). Transformations involving an alternative attack at the enol carbon center (bromination, selenation) have also been defined. Sodium borohydride reduction operates from the β-face of C-14 as long as the C-1 hydroxyl is not protected so as to offer steric exclusion. Complications associated with various aspects of these methodological undertakings are addressed. The most advanced oxygenation achievements were realized by way of a noteworthy sequence involving epoxidation of the O-methyl ether, methanolysis under mildly acidic conditions, and regioselective oxidation of diol 38 to give 39.