Synthesis of the Branched C-Glycoside Substructure of Altromycin B

Abstract

Tungsten-catalyzed cycloisomerization of alkynyl alcohols including 8 provides only the endocyclic enol ether (11) as a key intermediate for the branched C-glycoside substructure (2) of altromycin B. A sequence of Stille cross-coupling reaction and regio-and stereoselective functional group transformations affords each C13-diastereomer of the branched C-arylglycoside (2a and 2b).Altromycin B (1, Figure 1), a member of the family of pluramycin antibiotics isolated from a South African bushveld soil, was first reported to have selective antibiotic activities against Gram-positive bacteria in the early 1990s and later reported to possess anticancer activity including in vivo activity against P388 leukemia, as well as colon, lung, and ovarian tumors. 1 The structure of altromycin B has been elucidated primarily by NMR spectroscopy, and thus the absolute stereochemistry of each of the widely separated chiral subunits has not been unambiguously assigned. Along with the studies on the biological activities, interactions between altromycin B with DNA 2 and its metal complex 3 have been reported. Despite the attractive biological activity of altromycin B and various congener natural products, none of the altromycin natural products have been prepared by total synthesis. Pasetto and Franck recently reported the synthesis of both possible C13 isomers (2a, 2b) of the northwest quadrant of altromycin B, beginning with D-glucose. 4 However, their efforts to assign C13 stereochemistry on the basis of the NMR comparison of their synthetic compounds 2a and 2b with altromycin B (1) were unsuccessful because of the complexity of the natural product structure. In support of our ongoing studies directed at the total synthesis of altromycins, we report herein a different synthesis of substructures 2a and 2b arising from non-carbohydrate precursors. 5Our retrosynthetic analysis of 2a and 2b ( Figure 1) envisioned a cross-coupling reaction 6 to form the C13 1,1-methylene linking the carbohydrate and aglycone sectors in 3, with the fmcdona@emory.edu Supporting Information Available: Experimental procedures and characterization data for new compounds, including data in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org. carbohydrate coupling product 4 arising from the product of tungsten-catalyzed alkynol cycloisomerization of 5. 7 NIH Public AccessOur synthesis began with the known diol 6 (Scheme 1). 7a We observed regioselective formation of the methyl ether from the propargylic alcohol using cyclic stannylene activation of the diol, followed by silylation of the remaining alcohol and removal of the benzoate protective group with DIBAL reduction to afford alkynyl alcohol 7. Alternatively, protection of diol 6 with 2,2-dimethoxypropane in the presence of catalytic p-TsOH, followed by DIBAL reduction of the benzoate ester provided the cyclic acetonide-protected alkynol 8.The tungsten-catalyzed cycloisomerization was initially conducted with substrate 7 (Table 1). In contrast to other alk...

Transition metals in organic synthesis: Highlights for the year 2005

“…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]<...>…”

“…Tungsten catalyzed cycloisomerizations of a 1-yne-5-ols were used in syntheses toward altromycin B (Eq. (264)) [69] and erythro-4-deoxyglycals [1342]. Silver catalyzed cycloisomerizations of 6-and 7-ynals to give ketone-substituted five-and six-membered rings (Eq.…”

Brønsted Acid‐Mediated Hydrative Arylation of Unactivated Alkynes

“…Conversely,t ungsten [12] andr uthenium catalyzet he anti-Markovnikovh ydration of alkynes, [13] whereas titanium is able to selectively yield both products. [14] This reaction forms ac ritical link between alkyne and carbonyl chemistries.…”

Recent Advances in C-Glycoside Chemistry: Application, Synthesis and Reactions

“…[167][168][169][170][171][172][173] Os glicais halogenados ou os estanil-glicais atuam como substratos potenciais no acoplamento de Stille com organoestanho ou organohaletos para fornecer C-glicosídeos. [174][175][176][177][178][179][180] Por outro lado, C-glicosídeos também pode ser sintetizado pela reação de acoplamento de Negishi de um composto de organozinco ou um halogeneto orgânico, catalisado por complexos de níquel ou paládio. [181][182][183]…”