Total Synthesis of Mycalamide A. Further Synthetic Study of the Right Half

Nakata, Tadashi; Fukui, Hideto; Nakagawa, T.; Matsukura, Hiroko

doi:10.3987/com-95-s64

Cited by 26 publications

(16 citation statements)

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“…TBAF (22 mg, 70 µmol) was added to a solution of 18-O-TBS mycalamide B in THF (1 ml) and after 1 h at rt the reaction mixture was diluted with Et 2 O (5 ml) and washed with saturated aqueous NaHCO 3 (2 ml). The aqueous phase was extracted with CH 2 Cl 2 (2 × 5 ml) and the combined organic layers dried (Na 2 SO 4 ) and concentrated in vacuo to give an oil which was purified by column chromatography on silica gel 2C), 29 The structure and absolute stereochemistry of 60 was confirmed by X-ray crystallography with Mo X-rays on a CAD4 diffractometer. 90, 91 Crystal data ( 60 L-Selectride (1 M in THF, 0.27 ml, 0.27 mmol) was added dropwise to a solution of ketone 60 (85 mg, 0.144 mmol) in THF (2.7 ml) at Ϫ95 ЊC over 15 min.…”

Section: Formation Of Adduct 55mentioning

confidence: 99%

See 1 more Smart Citation

Synthetic studies on the pederin family of antitumour agents. Syntheses of mycalamide B, theopederin D and pederin

Kocieński

Narquizian

Raubo

et al. 2000

J. Chem. Soc., Perkin Trans. 1

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Section: Formation Of Adduct 55mentioning

confidence: 99%

“…2R,3R,4R)-2,3-Dimethyl-4-(phenylselanylmethyl)-6-trimethylstannyl-3,4-dihydro-2H-pyran (27)The conversion of lactone 26 (150 mg, 0.50 mmol) to 27 (156 mg, 0.35 mmol) was accomplished in 70% yield according to a reported procedure 26. Ethyl 6-chloro-2,2-dimethyl-3-oxohexanoate(29) …”

mentioning

confidence: 99%

Synthetic studies on the pederin family of antitumour agents. Syntheses of mycalamide B, theopederin D and pederin

Kocieński

Narquizian

Raubo

et al. 2000

J. Chem. Soc., Perkin Trans. 1

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“…All members of the pederin family are rare, difficult to isolate, and comparatively frail; many of them have potent and potentially useful activity as antiviral and antitumor agents (see below); this has stimulated considerable interest in their total synthesis. Total syntheses of pederin (Matsuda et al 1982(Matsuda et al , 1983(Matsuda et al , 1988Nakata et al 1985a,b;Willson et al 1987;larowicki et al 1990;Kocienski et al 1991Kocienski et al , 1998a , mycalamide A (Hong and Kishi 1990;Nakata et al 1994Nakata et al , 1996, mycalamide B (Hong and Kishi 1990;Kocienski et al 1998b), onnamide A (Hong and Kishi 1991), and theopederin D (Kocienski et al 1998a) have been reported, as have significant syntheses of various fragments (Nakata et al 1994;Isaac and Kocienski 1982;Isaac et al 1983;Kocienski and Willson 1984;Matsumoto et al 1984;Willson et al 1990a,b;Schlapbach 1992, 1993;Roush and Marron 1993;Toyota et al 1995Toyota et al , 1998aMarron and Roush 1995;Roush et al 1997;Breitfelder et al 1998;Trotter et al 1999). The parent member of the family, pederin itself, is also the simplest.…”

Section: Synthetic Studiesmentioning

confidence: 99%

“…Owing to competing decomposition, the reaction was stopped at approximately 60% completion to yield the epimerized natural diastereoisomer 37 in 42% yield along with the unnatural diastereoisomer 35 (33% yield). Nakata has also described a synthesis of mycalamide A in which the N-acyl aminal bridge is constructed by the Kishi procedure (Nakata et al 1996).…”

Section: The C8-n9 Connection Via Aminal Acylationmentioning

confidence: 99%

The Pederin Family of Antitumor Agents: Structures, Synthesis and Biological Activity

Narquizian¹,

Kocieński²

2000

The Role of Natural Products in Drug Discovery

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“…[3][4][5][6][7] The potent antitumour and antiviral activities of the marine compounds has stimulated interest in their synthesis because they are only available in minute amounts from natural sources. Total syntheses have been reported for pederin itself, [8][9][10][11] mycalamides A [12][13][14] and B 14,15 , and onnamide A. 16 Progress towards theopederin derivatives has been recorded 17,18 but no total syntheses have yet appeared.…”

mentioning

confidence: 96%

A Synthesis of Theopederin D and a Formal Synthesis of Pederin

Kocieński¹,

Narquizian²,

Raubo³

et al. 1998

Synlett

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Theopederin D, a cytotoxic metabolite from a sponge of the genus Theonella, was synthesised in 14 steps (11.1% overall yield) from two advanced intermediates previously used in a synthesis of mycalamide B. A formal synthesis of pederin from similar intermediates is also reported.Pederin (1) was the first and simplest member of a family of secondary metabolites which comprises the mycalamides, onnamides and theopederins. Though pederin was isolated from an insect (Paederus fuscipes), 1,2 all the subsequent structures were isolated from sponges of the genus Mycale or Theonella. [3][4][5][6][7] The potent antitumour and antiviral activities of the marine compounds has stimulated interest in their synthesis because they are only available in minute amounts from natural sources. Total syntheses have been reported for pederin itself, 8-11 mycalamides A 12-14 and B 14,15 , and onnamide A. 16 Progress towards theopederin derivatives has been recorded 17,18 but no total syntheses have yet appeared. We recently devised a general approach to all known members of the pederin family based on the metallated dihydropyran 2 (Scheme 1), which is a precursor to the 'left-half' common to all members of the pederin family, and the dihydropyranone 3, a platform designed for side-chain variation (Note 1). Our strategy was exemplified in a synthesis of mycalamide B (4) 15 in which the trioxadecalin intermediate 5 was fabricated from the dihydropyranone 3, and we now Scheme 1Downloaded by: University at Buffalo (SUNY). Copyrighted material. December 1998SYNLETT 1433 disclose the first synthesis of a member of theopederin family, theopederin D (6) which likewise uses trioxadecalin intermediate 5.To further underscore the flexibility of our general strategy, we also report the conversion of dihydropyranone 3 to the amide 7, a key pederin intermediate. Theopederin DOur synthesis of theopederin D began with the reductive cleavage of the pivalate ester in 5 (Scheme 2) using Red-Al followed by oxidation of the primary alcohol with pyridinium dichromate to give the carboxylic acid 8. A crucial step of the synthesis, introduction of the aminal centre at C10, was performed using a Curtius rearrangement as described by Roush 19 in order to secure the stereochemistry at the aminal centre unambiguously. The sequence entailed preparation of the acyl azide by reaction of carboxylic acid 8 with diphenylphosphoryl azide followed by thermolysis in the presence of 2-(trimethylsilyl)ethanol to trap the intermediate isocyanate as its 2-(trimethylsilyl)ethyl carbamate 9. No epimerisation of the aminal centre was observed. Acylation of the carbamate 9 with methyl oxalyl chloride in the presence of DMAP occurred slowly but cleanly to give the N-acyl oxalamide 10 in 70% yield. The crucial oxalamide ester 11 (Note 2) was then released by fluoride-induced cleavage of the 2-(trimethylsilyl)ethyl carbamate 10. 20The bridge linking the two ring systems was created by reaction of the oxalamide ester 11 with 3 equivalents of the lithiated dihydropyran 2 in the prese...

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Total Synthesis of Mycalamide A. Further Synthetic Study of the Right Half

Cited by 26 publications

References 0 publications

Synthetic studies on the pederin family of antitumour agents. Syntheses of mycalamide B, theopederin D and pederin

Synthetic studies on the pederin family of antitumour agents. Syntheses of mycalamide B, theopederin D and pederin

The Pederin Family of Antitumor Agents: Structures, Synthesis and Biological Activity

A Synthesis of Theopederin D and a Formal Synthesis of Pederin

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