Total Synthesis of Methyl Sarcophytoate, a Marine Natural Biscembranoid

Abstract

The total synthesis of methyl sarcophytoate (1), a marine natural biscembranoid, has been achieved by the thermal Diels-Alder reaction between the 14-membered dienophile unit, methyl sarcoate (2), and the 14-membered diene unit 64. Methyl sarcoate (2) was prepared using n-BuLi-Bu(2)Mg-mediated dithiane coupling, Kosugi-Migita-Stille coupling, and Grubbs ring-closing metathesis. The diene unit 64 was prepared using Sharpless asymmetric epoxidation, Grubbs ring-closing metathesis, 6-exo-tet epoxide opening, and n-BuLi-Bu(2)Mg-mediated Ito-Kodama cyclization. The final Diels-Alder reaction between 2 and 64 proceeded with high site, endo/exo, pi-face, and regioselectivities. During this reaction, partial E --> Z isomerization at the C4 position was observed.

Iron‐Catalyzed Highly Enantioselective cis‐Dihydroxylation of Trisubstituted Alkenes with Aqueous H2O2

“…Fumaric‐acid‐derived trisubstituted alkenes are important synthons in the synthesis of excitatory amino acid transporter inhibitors such as aspartate derivatives and natural products such as chaetomellic acid A anhydride and methyl sarcophytoate . The AD reactions of this type of alkenes are rare, which have application in synthesizing drug constituents such as piscidic acid; as a reported example, the AD reaction of ( E )‐MeO 2 C(CH 2 Ar)C=CHCO 2 Me (Ar= p ‐( t BuMe 2 Si)C 6 H 4 ) catalyzed by osmium compound (with K 3 Fe(CN) 6 as oxidant) afforded the cis ‐diol product with up to 83 % ee .…”

New Biscembranoids Sardigitolides A–D and Known Cembranoid-Related Compounds from Sarcophyton digitatum: Isolation, Structure Elucidation, and Bioactivities

“…The remaining compounds did not show any effective cytotoxic and anti-inflammatory activities. Methyl tortuosoate, also called methyl tetrahydrosarcoate (10) (Figure 4), has been frequently discovered to be the dienophile monomeric cembranoid in the Diels-Alder reaction to biosynthesize relevant biscembranoid, while methyl sarcoate (11) has been found to be the dienophile part of this series biscembranoids for only one time [37]. Biscembranoids 1 and 4 are the Diels-Alder reaction products using (7Z,8)-dehydromethyl tortuosoate (12), 2 using (7E,8)-dehydromethyl tortuosoate (13), and 3 using (7,19)-dehydromethyl tortuosoate (14), respectively, as the dienophiles in the biscembranoids biosynthesis.…”

Synthetic Applications of Chiral Unsaturated Epoxy Alcohols Prepared by Sharpless Asymmetric Epoxidation

“…Nakata et al [ 37 ] used the same transformation in their synthesis of a lactone fragment ( 79 ) (and synthetic precursor) of the marine biscembranoid methyl sarcophytoate ( Scheme 11 ). The enantiomerically enriched epoxy alcohol (3 S )-26 was treated with iodine, triphenylphosphine and imidazole to provide epoxy iodide 75 , which was treated with n -BuLi to give the allylic alcohol 76 .…”