Stereoselective Total Synthesis of (+)-Scyphostatin via a π-Facially Selective Diels−Alder Reaction

• Published in: Journal of organic chemistry Vol. 72; no. 11; pp. 4117 - 4125
• Main Authors: Takagi, Ryukichi, Miyanaga, Wataru, Tojo, Kengo, Tsuyumine, Shinjiro, Ohkata, Katsuo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.05.2007; Amer Chemical Soc
• Subjects: Amides - chemical synthesis; Amides - chemistry; Chemistry; Chemistry, Organic; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Molecular Conformation; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Pyrones - chemical synthesis; Pyrones - chemistry; Science & Technology; Stereoisomerism; APLYSINA-GERARDOGREENI; ASYMMETRIC-SYNTHESIS; HIPPOSPONGIC ACID; SCYPHOSTATIN SIDE-CHAIN; MODEL-COMPOUND; ENANTIOCONTROLLED SYNTHESIS; TRICHOPEZIZA-MOLLISSIMA; EFFICIENT ROUTE; RHOPALOIC ACID; NEUTRAL SPHINGOMYELINASE INHIBITOR; Tyrosine; Epimer; Diels Alder addition; Hydrophobic compound; Lactone; Selectivity; Stereochemistry; Oxygen heterocycle; Spiran; Total synthesis; Stereoselectivity; α-Aminoacid; Side chain; Aminoacid; Epoxide; Epoxidation; Hydrophilic compound; Chemical synthesis; Diastereomer
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo070337k

A stereoselective total synthesis of scyphostatin is described. The hydrophilic moiety was stereoselectively synthesized via (i) a highly π-facially selective Diels−Alder reaction of a spirolactone generated from l-tyrosine and (ii) a hydroxy group directed epoxidation as key reactions. The hydrophilic moiety was combined with the hydrophobic side chain in the final stage. Total synthesis was achieved by overcoming the instability of the C5−C6 epoxide ring with carefully executed mild reactions. In the course of this work, it was revealed that we had mistakenly assigned the relative stereochemistry of the C5−C6 epoxide ring of the end product in our previous model study. Revision of the stereochemical assignment in the model study is described. A diastereomer of (+)-scyphostatin epimeric at C5 and C6 (the epoxide region) was also synthesized.