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Volumn 121, Issue 28, 1999, Pages 6563-6579

The total synthesis of eleutherobin

Author keywords

[No Author keywords available]

Indexed keywords

DISCODERMOLIDE; ELEUTEROBIN; NATURAL PRODUCT; PACLITAXEL; SARCODICTYIN A; UNCLASSIFIED DRUG;

EID: 0033591877     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja990215c     Document Type: Article
Times cited : (142)

References (98)
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    • Near the end of the course of our studies (see ref 13), the total syntheses of sarcodictyins, eleutherobin, and eleuthosides were described by Professor K. C. Nicolaou and colleagues, (a) For the total synthesis of sarcodictyin A, see: Nicolaou, K. C.; Xu, J. Y.; Kim, S.; Pfefferkorn, J.; Ohshima, T.; Vourloumis, D.; Hosokawa, S. J. Am. Chem. Soc. 1998, 120, 8661. (b) For the total syntheses of eleutherobin and eleuthosides, see: Nicolaou, K. C.; van Delft, F.; Ohshima, T.; Vourloumis, D.; Xu, J. Y.; Hosokawa, S.; Pfefferkorn, J.; Kim, S.; Li, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 2520. Nicolaou, K. C.; Ohshima, T.; Hosokawa, S.; van Delft, F.; Vourloumis, D.; Xu, J. Y.; Pfefferkorn, J.; Kim, S. J. Am.Chem. Soc. 1998, 120, 8674.
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    • Near the end of the course of our studies (see ref 13), the total syntheses of sarcodictyins, eleutherobin, and eleuthosides were described by Professor K. C. Nicolaou and colleagues, (a) For the total synthesis of sarcodictyin A, see: Nicolaou, K. C.; Xu, J. Y.; Kim, S.; Pfefferkorn, J.; Ohshima, T.; Vourloumis, D.; Hosokawa, S. J. Am. Chem. Soc. 1998, 120, 8661. (b) For the total syntheses of eleutherobin and eleuthosides, see: Nicolaou, K. C.; van Delft, F.; Ohshima, T.; Vourloumis, D.; Xu, J. Y.; Hosokawa, S.; Pfefferkorn, J.; Kim, S.; Li, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 2520. Nicolaou, K. C.; Ohshima, T.; Hosokawa, S.; van Delft, F.; Vourloumis, D.; Xu, J. Y.; Pfefferkorn, J.; Kim, S. J. Am.Chem. Soc. 1998, 120, 8674.
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    • Some of the results contained herein were published as preliminary communications shortly after the publication of the first total synthesis of eleutherobin (ref 12b): (a) Chen, X.-T.; Zhou, B.; Bhattacharya, S. K.; Gutteridge, C. E.; Pettus, T. R. R.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1998, 37, 789. (b) Chen, X.-T.; Gutteridge, C. E.; Bhattacharya, S. K.; Zhou, B.; Pettus, T. R. R.; Hascall, T.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1998, 37, 185.
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    • Some of the results contained herein were published as preliminary communications shortly after the publication of the first total synthesis of eleutherobin (ref 12b): (a) Chen, X.-T.; Zhou, B.; Bhattacharya, S. K.; Gutteridge, C. E.; Pettus, T. R. R.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1998, 37, 789. (b) Chen, X.-T.; Gutteridge, C. E.; Bhattacharya, S. K.; Zhou, B.; Pettus, T. R. R.; Hascall, T.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl. 1998, 37, 185.
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    • note
    • The fact the two isomers in question were indeed stereoisomers and not regioisomers was proven by HMBC assignments on both 8 and 21.
  • 45
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    • note
    • The 1.3:1 ratio reflects a ratio of 28:[29 + 30].
  • 54
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    • note
    • 1D-selective NOESY on the lactone, 30, led to the assignment of the critical C8 center. The C8, C10, and C1 H's showed mutual NOE enhancement upon irradiation of each individual one. Furthermore, the C1 H and the isopropyl methyls showed enhancement, thus proving that the C1 H and therefore C10 and C8 as well were all β. (figure presented)
  • 55
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    • note
    • We considered the possibility of integrating the C8-R products (29 and 30) into the main synthetic stream. As shown in Scheme 1, 30 could be converted to 29. Indeed the oxidation of 29 could be conducted but the resultant ketone gave a mixture of streosiomers at C8 upon attempted reduction under several conditions.
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    • 3SnCl. A 6:1 ratio of the stannylated and the debrominated compound resulted. These could be separated by chromatography.
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    • note
    • A 15:1 mixture of isomers at C3 favoring the 3R isomer was obtained.
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    • See ref 17b
    • (a) See ref 17b.
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    • note
    • rel (kcal/mol) = 0 (out-out), 12.35 (H in-OTMS out); 14.33 (H out-OTMS in).
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    • At this stage we inferred that the geometry of the vinyl triflate to be E as shown in 58. A key point in the argument was the comparison of the C2-H in the NMR spectrum of the vinyl triflate with that of the corresponding H in the α,β-unsaturated aldehyde i (derived from the ketone 52, see Supporting Information for details). This was accomplished in a two-step procedure consisting of methoxymethylenation and a subsequent Conia reaction with singlet oxygen, see: Rousseau, G.; LePerchec, P.; Conia, J. M. Synthesis 1978, 67. Thus, an NOE enhancement between C2-H and C5-H was observed in i but not in the vinyl triflate 58, implying that the C2-C3 double bond in i is Z and by inference E in the vinyl triflate (see structure 58). Rigorous proof as to the correctness of the assignment was achieved when the total synthesis of eleutherobin was accomplished. (figure presented)
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    • For selective alkyl transfer to a vinyl iodide using internal coordination at tin, see: Vedejs, E.; Haight, A. R.; Moss, W. O. J. Am. Chem. Soc. 1992, 114, 6556.
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    • (a) Tri-O-acetyl thioethyl L-arabinoside has been described before: Pakulski, Z.; Pierozynski, D.; Zamojski, A. Tetrahedron 1994, 50, 2975. (b) For a suitably protected thiophenyl arabinoside, see: Nicolaou, K. C.; Trujillo, J. I.; Chibale, K. Tetrahedron 1997, 53, 8751. (c) Also see ref 12b.
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    • Also see ref 12b
    • (c) Also see ref 12b.
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    • By conventions of carbohydrate nomenclature, descriptors α and β in the arabinose series define the configurational relationship between C1 and C4 of the pyranoside. For the nomenclature of carbohydrates, see: McNaught, A. D. Carbohydr. Res. 1997, 297, 1. In terms of the structures presented here, a would correspond to the equatorial anomer and β to the axial one.
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    • For discussions on role of LiCl as an additive in Stille reactions, see: (a) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 54. (b) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (c) Reference 33b.
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    • For discussions on role of LiCl as an additive in Stille reactions, see: (a) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 54. (b) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (c) Reference 33b.
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    • Farina, V.1    Krishnan, B.2
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    • Reference 33b
    • For discussions on role of LiCl as an additive in Stille reactions, see: (a) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 54. (b) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (c) Reference 33b.
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    • See ref 10a
    • (a) See ref 10a.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.