| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1347524 | Tetrahedron: Asymmetry | 2008 | 9 Pages |
Convergent syntheses of (14R,15)- and (14S,15)-dihydroxycystothiazole A 4 were achieved based on a Julia-Kocienski coupling between the functionalized aldehyde (2E)-6 or (2Z)-6, corresponding to the left-side, and chiral sulfones (14R)-16 and (14S)-16, bearing a bithiazole moiety corresponding to the right-side, respectively. The absolute configuration of natural (14,15)-dihydroxycystothiazoles A 4 was determined to be (4R,5S,14S) by comparison of the physical data, including the sign of specific rotation, between synthetic (2E,4R,5S,6E,14S)-4 and natural 4. Deprotections of the silyl group and cyclopentane moiety of the coupled product (2E,4R,5S,6E,14R)-17 gave (14R,15)-dihydroxycystothiazole C 5, which was consistent with natural 5 corresponding to the minor isomer, including the sign of specific rotation. Likewise, deprotection of the silyl group and cyclopentane moiety of the coupled product (2E,4R,5S,6E,14S)-17 afforded (14S,15)-dihydroxycystothiazole C 5, which was consistent with natural 5 corresponding to the major isomer, including the sign of specific rotation. Finally, convergent synthesis of 14-hydroxycystothiazole C 3 was achieved based on the modified (one-pot) Julia olefination between the aldehyde (2Z)-6 and bithiazole sulfone 22. The absolute configurations of natural 14-hydroxycystothiazole C 3 were confirmed to be (4R) and (5S). Methylation of synthetic 3 gave cystothiazole B 2.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
14-Hydroxycystothiazole CC19H24N2O5S2[α]D22=+112.6 (c 1.17, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S)
(14R,15)-Dihydroxycystothiazole AC20H26N2O6S2[α]D23=+113.0 (c 0.76, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14R)
(14S,15)-Dihydroxycystothiazole AC20H26N2O6S2[α]D24=+77.8 (c 0.675, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14S)
(14R,15)-Dihydroxycystothiazole CC19H24N2O6S2[α]D24=+145.9 (c 0.64, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14R)
(14S,15)-Dihydroxycystothiazole CC19H24N2O6S2[α]D25=+91.1 (c 1.00, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (4R,5S,14S)
