The Total Synthesis of Both Enantiomers of the Macrocyclic Lactone Zearalane

Abstract

A straightforward approach to both enantiomers of zearalane is described from the enantiomerically pure alkenol (S)-4, prepared by a kinetic enzymatic resolution of the racemate. The key step is a Pd-catalyzed cross-coupling of an arene trifluoromethanesulfonate with a 9-alkyl-9-borabicyclo-

Macrolactonizations in the Total Synthesis of Natural Products

“…This reaction has been used in a number of 11- to 16-membered macrolactones, ,,− in the total syntheses of natural products such as (+)-amphidinolide K (eq a in Scheme ), 19-epi-avermectin B 1 , (+)-brefeldin C, citreofuran, antibiotics derived from erythromycin, , (+)-gloeosporone, − hypothemycin, cyclothialidine, lasiodiplodin, lobotamide C, ,, latrunculins A and B, − laulimalide, − where Yamaguchi and Keck methodologies result in Z / E isomerization of the conjugated double bond (eq b in Scheme ), leucascandrolide A, − (+)-milbemycin β 3 , , (+)-patulolide, suspensolide, , diolides UK-2A and UK-3A, , verrucarin A, zearalane, and aplyronine A analogues, in the total synthesis of griseoviridin, and in several approaches to its thiolactone core, − where, in particular, a highly strained nine-membered lactone has been obtained by Pancrazi 588 (see eq c in Scheme ). This methodology has also been successfully used in the syntheses of various cyclodepsipeptides as illustrated in Scheme . ,,−

69

…”

“…This reaction has been used in a number of 11-to 16membered macrolactones, 186,225,[551][552][553][554] in the total syntheses of natural products such as (+)-amphidinolide K 555 (eq a in Scheme 69), 19-epi-avermectin B 1 , 556 (+)-brefeldin C, 557 citreofuran, 558 antibiotics derived from erythromycin, 559,560 (+)-gloeosporone, [561][562][563] hypothemycin, 564 cyclothialidine, 565 lasiodiplodin, 123 lobotamide C, 70,513,566 latrunculins A and B, [567][568][569][570][571] laulimalide, [572][573][574] where Yamaguchi and Keck methodologies result in Z/E isomerization of the conjugated double bond (eq b in Scheme 69), leucascandrolide A, [575][576][577] (+)-milbemycin β 3 , 578,579 (+)-patulolide, 580 suspensolide, 581,582 diolides UK-2A and UK-3A, 583,584 verrucarin A, 585 zearalane, 586 and aplyronine A analogues, 361 in the total synthesis of griseoviridin, 587 and in several approach...…”

Update 1 of: Macrolactonizations in the Total Synthesis of Natural Products

“…This reaction has been used in a number of 11- to 16-membered macrolactones, ,,− in the total syntheses of natural products such as (+)-amphidinolide K (eq a in Scheme ), 19- epi -avermectin B 1 , (+)-brefeldin C, citreofuran, antibiotics derived from erythromycin, , (+)-gloeosporone, − hypothemycin, cyclothialidine, lasiodiplodin, lobotamide C, ,, latrunculins A and B, − laulimalide, ,, where Yamaguchi and Keck methodologies result in Z / E isomerization of the conjugated double bond (eq b in Scheme ), leucascandrolide A, − (+)-milbemycin β 3 , , (+)-patulolide, suspensolide, , diolides UK-2A and UK-3A, , verrucarin A, zearalane, and aplyronine A analogues, a formal synthesis of apicularen A, queenslandon, , retipolide E and ornatipolide, tedanolide, , and xestodecalactone A …”

Cu(I)-Catalyzed Macrocyclic Sonogashira-Type Cross-Coupling

“…To further demonstrate the utility of the Cu-catalyzed macrocyclic Sonogashira-type strategy, the polyketide-derived product ( S )-zearalane was prepared, which has been reported to have interesting anabolic, estrogenic, anthelminthic, and immunomodulating properties (Scheme ) . The enantioenriched secondary alcohol 18 , prepared via known procedures, underwent Mitsunobu-type coupling with known acid 19 to provide the ester 20 (98% yield).…”