Total Synthesis of the Potent HIF-1 Inhibitory Antitumor Natural Product, (8R)-Mycothiazole, via Baldwin-Lee CsF/CuI sp(3)-sp(2)-Stille Cross-Coupling. Confirmation of the Crews Reassignment.
A convenient asymmetric total synthesis of the potent HIF-1 inhibitory antitumor natural product, (-)- or (+)-(8R)-mycothiazole (1), is described. Not only does our synthesis confirm the 2006 structural reassignment made by Crews ( Crews , P. , et al. J. Nat. Prod. 2006 , 69 , 145 ), it revises the [α]D data previously reported for this molecule in MeOH from -13.7° to +42.3°. The newly developed route to (8R)-1 sets the C(8)-OH stereocenter via Sharpless AE/2,3-epoxy alcohol reductive ring opening and utilizes two Baldwin-Lee CsF/cat. CuI Stille cross-coupling reactions with vinylstannanes 8 and 3 to efficiently elaborate the C(1)-C(4) and C(14)-C(18) sectors.
The School of Chemistry & Chemical Engineering and the Centre for Cancer Research and Cell Biology (CCRCB), the Queen's University Belfast , Stranmillis Road, Belfast BT9 5AG, Northern Ireland, United Kingdom.
Liping
L
Wang
The School of Chemistry & Chemical Engineering and the Centre for Cancer Research and Cell Biology (CCRCB), the Queen's University Belfast , Stranmillis Road, Belfast BT9 5AG, Northern Ireland, United Kingdom.
Karl J
KJ
Hale
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001688:Biological Products; D051793:Hypoxia-Inducible Factor 1; D013844:Thiazoles; C508681:mycothiazole