Synthesis of a C(1)–C(23) Fragment for Spirastrellolide E: Development of a Mechanistic Rationale for Spiroketalization

• Published in: Organic letters Vol. 17; no. 8; pp. 1898 - 1901
• Main Authors: Sokolsky, Alexander, Cattoen, Martin, Smith, Amos B
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.04.2015; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Letter; Macrolides - chemical synthesis; Macrolides - chemistry; Molecular Conformation; Physical Sciences; Science & Technology; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Stereoisomerism; NORTHERN-HEMISPHERE; STEREOCONTROLLED TOTAL-SYNTHESIS; A CONSTRUCTION; DEF-BIS-SPIROACETAL; CATALYZED CYCLIZATION; ANION RELAY CHEMISTRY; PART 2; COMPLETION; F METHYL-ESTER; SUBUNIT
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.5b00595

Synthetic analysis of spirastrellolide E envisioned to entail a cross-metathesis union of the northern and southern hemispheres followed by a Sharpless epoxidation/methylation sequence to achieve the C­(22,23) stereogenicity leads to the design of a C(1)–C(23) advanced southern hemisphere exploiting a gold-catalyzed directed spiroketalization as a key step. Stereochemical analysis of this strategic transformation provides insight on the impact of the directing group carbinol stereogenicity on the reaction efficiency and, in turn, permits the conversion of the minor isomer of the spiroketal precursor to the requisite congener for successful spiroketalization.