An approach to aliphatic 1,8-stereocontrol: diastereoselective syntheses of (±)-patulolide C and (±)-epipatulolide C

Abstract

The tin(iv) bromide promoted reaction of 7-hydroxy-7-phenylhept-2-enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1,8-diols 12 and so indirect methods were developed for aliphatic 1,8-stereocontrol to complete diastereoselective syntheses of (±)-patulolide C 1 and (±)-epipatulolide C 40. (5Z)-3,7-syn-7-(2-Trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was prepared from the tin(iv) chloride promoted reaction of 4-(2-trimethylsilylethoxy)methoxypent-2-enyl(tributyl)stannane 16 with acrolein (1,5-syn : 1,5-anti = 96 : 4). An Ireland-Claisen rearrangement of the corresponding benzoyloxyacetate 21 with in situ esterification of the resulting acid using trimethylsilyldiazomethane gave methyl (4E,7Z)-2,9-anti-2-benzyloxy-9-(2-trimethylsilylethoxy)methoxydeca-4,7-dienoate 22 together with 10-15% of its 2,9-syn-epimer 26, the 2,9-syn- : 2,9-anti-ratio depending on the conditions used. An 88 : 12 mixture of esters was taken through to the tert-butyldiphenylsilyl ether 38 of (±)-patulolide C 1 together with 6% of its epimer 39, by reduction, a Wittig homologation and deprotection/macrocyclisation. Following separation of the epimeric silyl ethers, deprotection of the major epimer 38 gave (±)-patulolide C 1. The success of 2,3-Wittig rearrangements of allyl ethers prepared from (5Z)-3,7-syn-7-(2-trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was dependent on the substituents on the allyl ether. Best results were obtained using the pentadienyl ether 56 and the cinnamyl ether 49 that rearranged with >90 : 10 stereoselectivity in favour of (1E,5E,8Z)-3,10-syn-1-phenyl-10-(2-trimethylsilylethoxy)methoxyundeca-1,5,8-trien-3-ol 50. This product was taken through to the separable silyl ethers 38 and 39, ratio 7 : 93 by regioselective epoxidation and alkene reduction using diimide, followed by deoxygenation, ozonolysis, a Wittig homologation and selective deprotection/macrocyclisation. Deprotection of the major epimer 39 gave (±)-epipatulolide C 40.

Structure, Absolute Configuration, and Conformational Study of 12-Membered Macrolides from the Fungus Dendrodochium sp. Associated with the Sea Cucumber Holothuria nobilis Selenka

“…These metabolites were reported to have phototoxic, ,, cytotoxic, antifungal, ,,, antibacterial, , and antiviral activities . The flexible ring system and the remarkable bioactivities of these metabolites have attracted great interest as targets for total synthesis. − In particular, a number of total syntheses of recifeiolide, − cladospolides, − and patulolides − have been reported.…”

Asymmetric Hydroformylation-Initiated Tandem Sequences for Syntheses of (+)-Patulolide C, (−)-Pyrenophorol, (+)-Decarestrictine L, and (+)-Prelog Djerassi Lactone

“…Exhibiting both antifungal and antibacterial activities, the patulolides have been the targets of several total syntheses. Some strategies for macrocycle formation include utilizing the Yamaguchi macrolactonization, ,,− Mitsunobu lactonization, Shiina lactonization, or ring-closing metathesis . The olefin has been constructed by various methods including Horner–Wadsworth–Emmons and Wittig olefinations , and a photochemical rearrangement of an epoxydiazomethyl ketone .…”

“…A small aliquot was removed and analyzed by 1 H NMR to confirm completion and obtain an accurate B:L ratio (B:L = 12:1 by 1 H NMR in C 6 D 6 RD = 10, 64 scans). Once under argon, the reaction was then transferred to a nitrogen line and trans-2-butenylpinacolato boronic ester (24) (1.6 mL, 7.8 mmol) was added at rt. The reaction was allowed to stir at ambient temperature for 24 h, transferred to a 100 mL round-bottom flask with methanol, concentrated, and purified via FCC (3−20% ethyl acetate/ hexanes) to yield 21 as a clear colorless oil which solidified upon standing (786 mg, 83%): R f = 0.…”