- Propene as an Atom-Economical Linchpin for Concise Total Synthesis of Polyenes: Piericidin A
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A concise and convergent total synthesis of piericidin A is disclosed. The synthesis hinges on the utilization of propene as a synthetic linchpin to merge the properly elaborated alkyne fragments, leading to the 1,3,6-triene motif of piericidin A. Utilization of propene as a unique alkene, capable of sequential coupling with two alkynes, is further illustrated in the context of various 1,3,6-triene products. The latter process proceeds with high atom economy and efficiently gives rise to complex frameworks from readily accessible alkyne substrates. This strategic C-C bond formation offers an orthogonal paradigm in the design of synthetic routes, leading to higher step economy and more efficient syntheses of polyunsaturated natural products.
- Trost, Barry M.,Gholami, Hadi
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supporting information
p. 11623 - 11626
(2018/09/21)
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- Polyketides and Anthranilic Acid Possessing 6-Deoxy-α- l -talopyranose from a Streptomyces Species
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A bioassay-guided investigation in conjunction with chemical screening led to the isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy-α-l-talopyranoside (2), and naphthomycinoside (3), along with three known secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures were elucidated by detailed NMR and MS spectroscopic analyses. Absolute configurational analysis of the sugar units based on the magnitudes of the coupling constants, NOESY correlations, chemical derivatization, and optical rotation measurements revealed that compounds 1-3 and 5 incorporate the rare deoxyhexose 6-deoxy-α-l-talopyranose. The absolute configuration of a polyketide extender unit of 3 was determined by applying the J-based configuration analysis and modified Mosher's method. Ulleungoside (1) and naphthomycin A (7) showed in vitro inhibitory effects against indoleamine 2,3-dioxygenase activity. Further bioevaluation revealed that compounds 1 and 7 had moderate antiproliferative activities against several cancer cell lines, and compounds 5 and 6, which are members of the piericidin family, induced autophagosome accumulation.
- Son, Sangkeun,Ko, Sung-Kyun,Jang, Mina,Lee, Jae Kyoung,Kwon, Min Cheol,Kang, Dong Hyo,Ryoo, In-Ja,Lee, Jung-Sook,Hong, Young-Soo,Kim, Bo Yeon,Jang, Jae-Hyuk,Ahn, Jong Seog
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p. 1378 - 1386
(2017/05/31)
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- Total synthesis of (+)-piericidin A1 and (-)-piericidin B1
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The convergent syntheses of (+)-piericidin A1 1 and (-)-piericidin B1 2 have been achieved based on classical Julia-Lythgoe olefination between 4-hydroxy-5,6-dimethoxy-3-methyl-2-[5-oxo-3-methyl-pent-(2E)-enyl]-pyridine 3 correspondi
- Kikuchi, Ryosuke,Fujii, Mikio,Akita, Hiroyuki
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experimental part
p. 1975 - 1983
(2010/03/04)
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- Total synthesis of piericidin A1 and B1 and key analogues
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Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation of a series of key analogues are described including ent-piericidin A1 (ent-1), 4′-deshydroxypiericidin A1 (58), 5′-desmethylpiericidin A1 (73), 4′-deshydroxy-5′- desmethylpiericidin A1 (75), and the corresponding analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues, along with those derived from their further functionalizations, permitted a scan of the key structural features providing new insights into the role of the substituents found in both the pyridyl core as well as the side chain. A strategic late stage heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain permitted ready access to the analogues in which each half of the molecule could be systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electron demand Diels-Alder reactions of N-sulfonyl-1-azabutadienes, while key elements of side chain syntheses include an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry (for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chains.
- Schnermann, Martin J.,Romero, F. Anthony,Hwang, Inkyu,Nakamaru-Ogiso, Eiko,Yagi, Takao,Boger, Dale L.
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p. 11799 - 11807
(2007/10/03)
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- Total synthesis of piericidin A1 and B1
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The first total syntheses of piericidin A1 and B1 are disclosed and unambiguously establish the relative and absolute stereochemistry of the natural products by an approach that will facilitate the synthesis of a series of analogues. Central to the approach is an inverse electron demand Diels-Alder reaction of a N-sulfonyl-1-aza-1,3-butadiene with tetramethoxyethene followed by Lewis acid-promoted aromatization used to assemble the functionalized pyridine core. Additional key elements in the convergent approach include the use of an anti-aldol reaction to install the C9 and C10 relative and absolute stereochemistry, a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chain, and a penultimate heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain. Copyright
- Schnermann, Martin J.,Boger, Dale L.
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p. 15704 - 15705
(2007/10/03)
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