Stereoselective Syntheses of Dihydroxerulin and Xerulinic Acid, Anti‐Hypocholesterolemic Dyes from the Fungus Xerula melanotricha

Abstract

The title compounds 2 and 3, which are inhibitors of the biosynthesis of cholesterol, were synthesized in a convergent and perfectly stereoselective manner. In the key step, bromobutenolide 6 (obtained from levulinic acid in two steps) was coupled with either of the novel bis(stannanes) trans,cis,trans-35 or trans,trans,trans-35 [each accessible from 3-(tributylstannyl)allyl alcohol (17) in four steps], giving gamma-alkylidenebutenolide trans,trans,trans-32. This compound was coupled with iododiyne 42 or the bromoenediynoate 44 leading to dihydroxerulin (2) and to the (trimethylsilylethyl)ester 45 of xerulinic acid, respectively. Deprotection of the latter provided totally synthetic xerulinic acid (3) for the first time.

Transition metals in organic synthesis: Highlights for the year 2005

“…Palladium complexes, together with a hydride source, such as tributyltin hydride, triethylsilane, and triethylamine-formic acid catalyzed the reduction organic bromides, iodides, and triflates. Synthetic applications include, 1,8-naphthyrine C-nucleosides [592], cylindramine [324], azadirachtin [593], dihydroxerulic and xerulinic acid [38], bergapten [594], 3-methoxyelipticine and elipticine [595], (−)-scabronine G [44], (−)-galanthamine and (−)-morphine [447], toward (+)-sorangicin [268], 2-fluoro-11-hydroxy-N-propylnoraporphine [596], hetsine alkaloids [597], pancracine [430] and the DEF-rings of FR182877 [598].…”

“…Palladium-catalyzed hydrostannations of terminal alkynes, using tributyltin hydride, to give alkenylstannanes were used in total synthesis toward peridinin [35], 6 -epi-peridinin [60], dihydroxerulic and xerulinic acid [38], (+)-tubelactomicin A [64,868] and macrolactin analogs [82]. Regioselective palladium-catalyzed hydrostannations of internal alkynes were used in synthesis toward mycolactones A and B [296], tricyclic core of GKK1032 [81], zoanthamine [83] and xanthocillin X dimethylether [87].…”

“…Synthetic targets include, the heterocyclic core of GE 2270 [34], peridinin [35], pyrones isolated from placobranchus ocellatus [36], terpenepolyketide natural products [37], dihydroxerulic and xerulinic acid [38], bipinnatin J [39], elipticine [40], (+)-7-deoxytrans-dihydronarciclasine [41], gambierol [42], taiwaniaquinol [43], (−)-scabronine G [44], garsubellin A [45], piericidin A1 and B1 [46], lucilactaene [47], fostriecin [48], lupine alkaloids [49], ␤-C-glycosides [50], (+)-crocacin D [51], lobatamide analogs [52], epoxyquinoid compounds [53,54], (+)-SCH 351448 [55], 3-methyl-2,5-dihydro-1-benzoxepin carboxylic acids [56], (+)-ochromycinone and (+)-rubiginone B 2 [57], EI-1941-1 and EI-1941-2 [58], mycothiazole [59], 6 -epiperidinin [60], aureothin and N-acylaureothamine [61], cyercene A and placidenes [62], herbindole B [63], (+)-tubelactomicin A [64], saudin [65], peroxyacarnoates A and D [66], aureothin, N-acetylaureothamine, aureonitrile [67], elysiapyrones [68], altromycin B [69], (+)-phorboxazole A and analogues [70,71], (−)-SNF4435 C and (+)-SNF4435 D [72], A2E [73], paracentrone [74]<...>…”

Recent Advances in the Stereochemical Determination and Total Synthesis of Myxobacterial Polyketides

“…It became obvious that the latter alternative was less effective, so usage of stannane 101 was pre- ferred. The preparation of 101 involved triene linker 102, which was prepared by Julia-Kociénski olefination according to the method reported by Brückner and co-workers, 74 while the required vinyl iodide 103 was accessible in six steps from commercially available (S)-dimethyl malate (117). Cross-coupling of bis-stannane 102 and iodide 103 gave the fully functionalized stannane 101 in good yield.…”

Stereocomplementary Syntheses of 1,ω‐DistannylatedE,Z‐Isomeric Conjugated Trienes, Tetraenes, and Pentaenes

“…The convergency of Stille coupling strategies increases when three components are involved and one is a 1,2‐distannylated ethene, 1,4‐distannylated buta‐1,3‐diene, or 1,ω‐distannylated linear conjugated polyene. In spite of this conceptional advantage, such tandem Stille couplings have been reported only occasionally, that is, for E ‐1,2‐bis(tributylstannyl)ethene a few times,3, 4 an isomeric mixture of 1,4‐bis(trimethylstannyl)buta‐1,3‐dienes in two studies,5 1,6‐bis(tributylstannyl)hexa‐1,3,5‐triene (all‐ E ‐ 2 ; Scheme ) as an intermediate for syntheses of xerulinic acid6–8 and xerulin,8 1,6‐bis(tributylstannyl)hepta‐1,3,5‐triene (all‐ E ‐ 9 ; see Scheme ) as an intermediate for pyrrhoxanthin,9 and 1,10‐bis(tributylstannyl)‐1,3,5,7,9‐decapentaene (mono‐ Z ‐ 32 ; see Scheme ) as an intermediate for β‐carotene 10. The respective distannanes in the cited examples linked two different electrophiles either intramolecularly3 or intermolecularly4f, 5a, 6–9 or two equivalents of a single electrophile 4a.…”