Absolute Configuration of TPU-0043, a Pentaene Macrolide from Streptomyces sp.

Igarashi, Yasuhiro; In, Yasuko; Ishida, Toshimasa; Fujita, Tsuyoshi; Yamakawa, Takashi; Onaka, Hiroyasu; Furumai, Tamotsu

doi:10.1038/ja.2005.71

Cited by 8 publications

(7 citation statements)

References 11 publications

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“…Moreover, if one accepts “configurational analogy for biosynthetic homology” as supporting evidence, the 3D structure of the polyol polyene macrolide antibiotic TPU‐0043 from Streptomyces sp. TP‐A0625 is constitutionally close to both filipin III ( 1 ) and pentamycin ( 2 ) 11. In TPU‐0043, C‐15 is configured such as implied by stereostructures ent ‐ 1 and ent ‐ 2 of Figure 1 11.…”

Section: Introductionmentioning

confidence: 99%

Stereocontrolled Synthesis of a C¹–C¹⁰ Building Block (“Southwestern Moiety”) for the Unnatural Enantiomers of the Polyene Polyol Antibiotics Filipin III and Pentamycin: A Sultone‐Forming Ring‐Closing Metathesis for Protection of Homoallylic Alcohols

Walleser

Brückner

2014

Eur J Org Chem

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In C2‐symmetric diol 10 one OH group was substituted by crotonic acid and the other was incorporated in an ethenesulfonate. A twofold ring‐closing metathesis under forcing conditions provided unsaturated lactone/unsaturated sultone 24. Conjugate addition of Li2(PhMe2Si)2Cu(CN) to both C=C bonds was followed by opening of the sultone moiety with Bu4N+F–. Resultant homoallylic alcohol 28 was carried on to acetonide‐containing lactone 31. Its CpTiCl2 enolate underwent a completely diastereoselective aldol addition to hexanal. Functional group interconversions rendered “southwestern” C1–C10 building block 37. The steps (1) ethenesulfonylation of a homoallylic alcohol, (2) sultone formation, (3) Li2(PhMe2Si)2Cu(CN) addition, and (4) alcohol release by fluoride‐induced fragmentation, from our main sequence represent a new protection/deprotection stragegy for a secondary homoallylic alcohol, as demonstrated with a model compound, too.

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Section: Introductionmentioning

confidence: 99%

Stereocontrolled Synthesis of a C¹–C¹⁰ Building Block (“Southwestern Moiety”) for the Unnatural Enantiomers of the Polyene Polyol Antibiotics Filipin III and Pentamycin: A Sultone‐Forming Ring‐Closing Metathesis for Protection of Homoallylic Alcohols

Walleser

Brückner

2014

Eur J Org Chem

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“…After being stirred for 3 h, the reaction medium was poured into saturated aqueous NH 4 Cl and the product was extracted with CH 2 Cl 2 (150 ml). The organic extract was washed with Brine, dried with Na 2 SO 4 , then filtered, and evaporated in vacuo.…”

Section: Methodsmentioning

confidence: 99%

“…[3][4][5][6][7] However the structure of 1 including the relative and absolute stereochemistry has not been fully elucidated yet. The potent biological activity and structural complexity of this compound prompted us to initiate synthetic studies toward 1.…”

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confidence: 99%

“…The addition of LiCl did not affect the yield of the aldol products 8 and 11 (entry 1). However, the addition of Me 2 AlCl, TiCl(OiPr) 3 , Sc(OTf) 3 , SnCl 4 or Sn(OTf) 2 , improved the yield of the products (entries 2, 4, 6, 8, 9). When Me 2 AlCl or TiCl(OiPr) 3 was used, the major product was 8 (entries 2, 4).…”

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confidence: 99%

“…With the triene 15 in hand, we next examined Stille coupling of 15 with vinyl stannane 5 which is bearing phospho- 4 as catalyst precursor, desired coupling product 4 was obtained in 42% yield and reductive product 16 in 12% yield in the presence of Pd 2 (dba) 3 . When AsPh 3 was added in the reaction mixture, the coupling product was obtained in 63% yield without accompanying an undesired 16.…”

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confidence: 99%

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Synthetic Study on Telomerase Inhibitor, D8646-2-6: Synthesis of the Key Intermediate Using Sn(OTf)2 or Sc(OTf)3 Mediated Aldol-Type Reaction and Stille Coupling

Kanai

Takeda

Kuramochi

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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In 2002, the Mitsubishi Pharma group reported the isolation of a telomerse inhibitor, D8646-2-6 (1) from the culture broth of fungus Epicoccum purpurascens.1) The compound has a unique C 3 -pyranosyl 4-hydroxypyrone moiety 2) and conjugated polyene unit. [3][4][5][6][7] However the structure of 1 including the relative and absolute stereochemistry has not been fully elucidated yet. The potent biological activity and structural complexity of this compound prompted us to initiate synthetic studies toward 1. In our preceding paper, we have reported the construction of the C-glycosyl 4-hydroxy pyrone moiety of 1. Comparison of the NMR spectra of the C 3 -galactopyranosyl 4-hydroxy-2-pyrone moiety 2 with those of natural 1, demonstrated that the carbohydrate moiety of the latter compound to be C 3 -galactopyranoside (Fig. 1). 8)Our synthetic strategy toward the total synthesis of 1 is shown in Chart 1. Due to the labile nature of the polyeninc side chain, our synthestic strategy involved an initial aldol condensation of the pyrone moiety with the side chain unit (C8-C12), followed by the elongation of the remaining side chain unit. Since the stereochemistry at C21 and C23 was not determined, we envisaged that phosphonate 4 would serve as a versatile key intermediate for the synthesis of D8646-2-6 and its stereoisomeres. Horner-Wadsworth-Emmons reaction was successfully utilized by Cha and co-workers in the total synthesis of citreoviridin 9) which contains polyene conjugated with pyrone ring. Phosphonate 4 could be synthesized by Stille coupling 10) of triene 15 with vinyl stannane which contains phosphonate. 11) Although there have been some reports concerning the aldol-type reaction and alkylation of pyrones, 12-24) the application of this approach to a carbohydrate-containing compound is unprecedented. Since oxygenated functionalities of substrates might influence on the reactivity of carbanion, the reactivity of such carbohyrare-bearing pyrones as well as its synthetic utilities is quite interesting. Herein, we report the synthesis of the key intermediate 4 using aldol-type reaction of carbohydrate containing pyrone 7 followed by stepwise dehydration and Stille coupling with vinyl stannane 5 which contains phosphonate group.The feasibility of the key aldol-type reaction was evaluated through model systems. The aldol-type reaction of 7 [25][26][27] with (2E,4E)-hexa-2,4-dienal by the simple treatment with LiHMDS to give 8 in only 6% yield and 62% of 7 was recovered (Chart 2).However, the aldol-type reaction of 4-methoxy-6-methyl-2-pyrone 9 with (2E,4E)-hexa-2,4-dienal proceeded smoothly under the same conditions to afford the aldol product 10 in 87% yield. These results indicated that the carbohydrate moiety greatly influenced the aldol-type reaction. We reasoned that the highly oxygenated functional group of 7 might decrease the reactivity of the pyrone-stabilized carbanion through the coordination to the lithium ion or by steric The synthesis of the key intermediate (4) in the proposed route to D8646-2-6 is desc...

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