The transacetoacetylation: Mechanistic implications.

Witzeman, J. S.

doi:10.1016/s0040-4039(00)88816-4

Cited by 47 publications

(24 citation statements)

References 9 publications

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“…Formation of an intermediate acylketene is followed by nucleophilic addition. 41 In the event, the β-keto ester 54 was heated at 110 °C in refluxing toluene, and macrolactone 55 was produced as a single diastereoisomer in 72% yield (Scheme 10). …”

Section: Resultsmentioning

confidence: 99%

Studies for the Total Synthesis of Amphidinolide P

Williams

Myers

et al. 2013

J. Org. Chem.

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A convergent, enantiocontrolled total synthesis of the 15-membered macrolide, amphidinolide P, is described. The synthesis utilizes three nonracemic components for an efficient assembly of the macrolactone in 12 steps via the longest linear pathway. Key developments include studies of the Hosomi–Sakurai reaction for the formation of the C6–C7 bond, a “ligandless” palladium-mediated Stille cross-coupling of the vinylic stannane 4 and the alkenyl bromide 5 to produce a highly functionalized dienol, and a thermally induced, intramolecular lactonization via the late-stage formation of an intermediate α-acylketene.

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Section: Resultsmentioning

confidence: 99%

Studies for the Total Synthesis of Amphidinolide P

Williams

Myers

et al. 2013

J. Org. Chem.

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“…48,49 Acylketenes may also be a key intermediate in the alcoholysis of dithiomalonates because of the inertness of α,α dimethylmalonate 75 and dithiosuccinate 76. Furthermore, kinetic studies on the reaction of 66 with n butanol under re ux conditions (82 ) in acetonitrile revealed that rate constants were independent of the concentration of n butanol.…”

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confidence: 99%

Synthesis of Xanthanolides Including New Acylations and Their Synthetic Applications

Shindo¹,

Matsumoto²

2013

J. Synth. Org. Chem. Jpn.

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“…The combined DCM filtrate and washings were evaporated to dryness. The residue was flash chromatographed (60g, SiO 2 , 50:1 DCM-CH 3 OH to afford 1.54 g (66%) of carboxylic acid 8 as a colorless oil: TLC R f 0.51 ( 1, 169.3, 156.5, 136.0, 128.6, 128.3, 128.1, 76.2, 70.7, 70.5, 69.5, 67.4, 57.6, 43.9, 36.5, 25.7, 24.4, 24.0, 23.4, 21.5, 18.1, 16.9, 16.7, 15.3, 11.5, -4.8, -5.5 7, 172.4, 169.7, 168.7, 167.3, 156.3, 136.0, 135.7, 133.1, 129.9, 128.6, 128.3, 128.1, 127.7, 78.6, 71.7, 70.7, 70.1, 67.3, 57.9, 56.4, 52.4, 46.0, 44.5, 39.2, 37.0, 29.7, 26.8, 24.8, 24.2, 24.1, 23.3, 22.9, 22.3, 21.4, 19.4, 16.9, 14.9, 11.4; FAB MS 961.4854 To amide 46 (0.367 g, 0.44 mmol) in CH 3 OH (5 mL) under N 2 at 0 °C was added acetyl chloride (50 μL, 69.5 mg, 0.88 mmol). The solution was stirred at ambient temperature for 30 min, diluted with DCM (40 mL), washed with 6% NaHCO 3 (20 mL) and H 2 O (10 mL), dried and NMR δ 201.7, 174.8, 169.3, 169.2, 168.6, 135.8, 128.6, 128.4, 128.2, 79.0, 78.8, 71.2, 69.9, 69.0, 68.9, 67.5, 57.5, 56.5, 56.4, 46.1, 42.8, 39.7, 36.8, 29.7, 24.9, 24.3, 24.3, 23.2, 21.5, 16.7, 14.8, 11.2; FAB MS 723.3735 204.5, 171.7, 170.1, 169.8, 167.7, 166.4, 156.7, 135.8, 128.6, 128.4, 128.2, 81.2, 72.4, 72.2, 71.3, 67.6, 57.8, 57.2, 47.0, 41.2, 39.2, 36.7, 25.3, 24.9, 24.4, 23.5, 22.8, 21.8, 20.8, 18.5, 16.4, 14.4, 10.6 …”

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“…Kitastatin 1 (1a) and respirantin (1b) contain a blastmycic acid unit also found in the antimycins 2 such as 2 and neoantimycin 3 . An unusual structural feature is the β-ketoester linkage (carbons [6][7][8] in the 18-membered depsipeptide macrocycle. In order to obtain sufficient material for more extensive biological evaluation as well as overall to determine the stereochemistry and absolute configuration of kitastatin 1 (1a) and respirantin (1b), we undertook research to develop a total synthesis of 1b with flexibility to enable future SAR development.…”

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Antineoplastic Agents. 561. Total Synthesis of Respirantin^1a

et al. 2007

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Total synthesis of the eighteen-membered ring cyclodepsipeptide believed to be respirantin (1b) has been achieved. The key step in the synthesis is an intramolecular transesterification of the β-ketoester alcohol 6 to afford the protected macrocycle 5. The synthetic product was shown to be identical to a natural product presumed to be respirantin (1b) and the absolute stereochemistry of 6 of the 7 asymmetric centers of cyclodepsipeptide 1b was unequivocally established. Respirantin (1b) was found to be a remarkable inhibitor of cancer cell growth and related to the antimycin family of antibiotics.In the preceding report, we summarized the isolation and structures of three exceptional cancer cell growth inhibitory cyclodepsipeptides from the bacterium Kitasatospora sp. found on the Beaufort Sea coast of the Alaska North Slope. 1a One of these corresponded to a unique structure and was designated kitastatin 1 (1a) (Figure 1) while the other two cyclodepsipeptides on the basis of reported NMR assignments were presumed to be respirantin (1b) and a valeryl modification (1c). 1b Respirantin (1b) was first reported in 1993 1b as an insecticidal antibiotic isolated from a Streptomyces species found in a soil sample from Japan and shown to have cyclodepsipeptide structure 1b based on analysis of its spectroscopic properties. The stereochemistry was not determined. Kitastatin 1 (1a) and respirantin (1b) contain a blastmycic acid unit also found in the antimycins 2 such as 2 and neoantimycin 3 . An unusual structural feature is the β-ketoester linkage (carbons 6-8) in the 18-membered depsipeptide macrocycle. In order to obtain sufficient material for more extensive biological evaluation as well as overall to determine the stereochemistry and absolute configuration of kitastatin 1 (1a) and respirantin (1b), we undertook research to develop a total synthesis of 1b with flexibility to enable future SAR development. Herein we report the successful results. Results and DiscussionInspection of the kitastatin 1 (1a) and respirantin (1b) macrocycle revealed that they are composed of common amino acids, or α-hydroxycarboxylic acids derived from them, along with the β-ketoester unit. Since the absolute stereochemistry of 1a and 1b was undetermined at the onset of this study, our initial target 1b was selected by assuming the most common Sconfiguration for the constituent amino acids and their presumed α-hydroxy derivatives. Fortunately, that proved to be the correct choice among the 256 possible optical isomers. A retrosynthetic analysis of the ultimately successful route to respirantin (1b) is presented in Scheme 1. Prior antimycin syntheses 2 offered good precedent for appending the protected benzoic acid 3 to amino substituted macrocycles. However other issues that needed to be * To whom correspondence should be addressed. Tel: (480) . E-mail: bpettit@asu.edu. NIH Public AccessAuthor Manuscript J Nat Prod. Author manuscript; available in PMC 2008 December 8. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Autho...

show abstract

The transacetoacetylation: Mechanistic implications.

Cited by 47 publications

References 9 publications

Studies for the Total Synthesis of Amphidinolide P

Studies for the Total Synthesis of Amphidinolide P

Synthesis of Xanthanolides Including New Acylations and Their Synthetic Applications

Antineoplastic Agents. 561. Total Synthesis of Respirantin^1a

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The transacetoacetylation: Mechanistic implications.

Cited by 47 publications

References 9 publications

Studies for the Total Synthesis of Amphidinolide P

Studies for the Total Synthesis of Amphidinolide P

Synthesis of Xanthanolides Including New Acylations and Their Synthetic Applications

Antineoplastic Agents. 561. Total Synthesis of Respirantin1a

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Antineoplastic Agents. 561. Total Synthesis of Respirantin^1a