Abstract:[reaction: see text] An S-phenyl alpha-D-idoseptanoside donor was used in the selective preparation of a series of alpha-D-idoseptanosyl glycosides. Glycosylation of a methyl beta-D-glycero-D-guloseptanoside acceptor with the new donor constituted the first synthesis of a septanose disaccharide.
“…The configuration of the newly formed C26 stereogenic center was determined by an NOE experiment, as shown in Figure 3, and the stereoselectivity of the allylation of 71 was in accordance with that observed for the O ‐glycosylation of septanosides 53. The stereochemical outcome can be explained by a stereoelectronic effect (Figure 4 A).…”
In this study, we report the first total synthesis and complete stereostructure of gambieric acid A, a potent antifungal polycyclic ether metabolite, in detail. The A/B-ring exocyclic enol ether 32 was prepared through a Suzuki-Miyaura coupling of the B-ring vinyl iodide 18 and the alkylborate 33 and subsequent closure of the A-ring by using diastereoselective bromoetherification as the key transformation. Suzuki-Miyaura coupling of 32 with acetate-derived enol phosphate 49, followed by ring-closing metathesis of the derived diene, produced the D-ring. Subsequent closure of the C-ring through a mixed thioacetalization completed the synthesis of the A/BCD-ring fragment 8. The A/BCD- and F'GHIJ-ring fragments (i.e., 8 and 9) were assembled through Suzuki-Miyaura coupling. The C25 stereogenic center was elaborated by exploiting the intrinsic conformational property of the seven-membered F'-ring. After the oxidative cleavage of the F'-ring, the E-ring was formed as a cyclic mixed thioacetal (i.e., 70) and then stereoselectively allylated by using glycosylation chemistry. Ring-closing metathesis of the diene 3 thus obtained closed the F-ring and completed the polycyclic ether skeleton. Finally, the J-ring side chain was introduced by using a Julia-Kocienski olefination in the presence of CeCl3 to complete the total synthesis of gambieric acid A (1), thereby unambiguously establishing its complete stereostructure. The present total synthesis enabled us to evaluate the antifungal and antiproliferative activities of 1 and several synthetic analogues.
“…The configuration of the newly formed C26 stereogenic center was determined by an NOE experiment, as shown in Figure 3, and the stereoselectivity of the allylation of 71 was in accordance with that observed for the O ‐glycosylation of septanosides 53. The stereochemical outcome can be explained by a stereoelectronic effect (Figure 4 A).…”
In this study, we report the first total synthesis and complete stereostructure of gambieric acid A, a potent antifungal polycyclic ether metabolite, in detail. The A/B-ring exocyclic enol ether 32 was prepared through a Suzuki-Miyaura coupling of the B-ring vinyl iodide 18 and the alkylborate 33 and subsequent closure of the A-ring by using diastereoselective bromoetherification as the key transformation. Suzuki-Miyaura coupling of 32 with acetate-derived enol phosphate 49, followed by ring-closing metathesis of the derived diene, produced the D-ring. Subsequent closure of the C-ring through a mixed thioacetalization completed the synthesis of the A/BCD-ring fragment 8. The A/BCD- and F'GHIJ-ring fragments (i.e., 8 and 9) were assembled through Suzuki-Miyaura coupling. The C25 stereogenic center was elaborated by exploiting the intrinsic conformational property of the seven-membered F'-ring. After the oxidative cleavage of the F'-ring, the E-ring was formed as a cyclic mixed thioacetal (i.e., 70) and then stereoselectively allylated by using glycosylation chemistry. Ring-closing metathesis of the diene 3 thus obtained closed the F-ring and completed the polycyclic ether skeleton. Finally, the J-ring side chain was introduced by using a Julia-Kocienski olefination in the presence of CeCl3 to complete the total synthesis of gambieric acid A (1), thereby unambiguously establishing its complete stereostructure. The present total synthesis enabled us to evaluate the antifungal and antiproliferative activities of 1 and several synthetic analogues.
“…We have also used 13 C chemical shifts as diagnostics for anomeric configuration of septanosides in previous systems. In the limited examples we have collected, 7,14,17,18 the trend is that d C1 of b-septanosides is slightly downfield relative to a-septanosides. The 13 C NMR measured values for d C1 of 3 is 106.1 ppm and that of 4 is 109.3 ppm.…”
Section: Determination Of Configurationmentioning
confidence: 91%
“…While a methyl group is perhaps a small surrogate for an oligosaccharide linked via a glycosidic bond, some prior reports with furanosides suggest that this model can provide a great insight. 14 Indeed, we were interested in determining if glycosylation at C5 of septanoses 1 and 2 would change the distribution of their preferred conformers as has been observed in other carbohydrate systems. 12 Defining diseptanoside structures that contain either an a-(1!5)-linkage or a b-(1!5)-linkage are valuable to us because they approximate the natural disaccharides maltose and cellobiose.…”
“…This approach is used extensively in carbohydrate chemistry, where a substituent at the 2-position, usually an acyloxy group, controls the stereochemical configuration of substitution. [2-4] An acyloxy group can form a fused ring system resembling 1 (Figure 1), and opening of the five-membered ring by a nucleophile installs the nucleophile trans to the participating group. [2,5] Acyloxy groups at remote positions can also exert influences on stereoselectivity.…”
Nucleophilic substitution reactions of acetals with benzyloxy groups four carbon atoms away can be highly diastereoselective. The selectivity in several cases increased as the reactivity of the nucleophile increased, in violation of the reactivity-selectivity principle. The increase in selectivity with reactivity suggests that multiple conformational isomers of reactive intermediates can give rise to the products.
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