Facile preparation of (2R,3S)- and (2S,3R)-3-[[(4-bromobenzyl)oxy]methyl]oxirane-2-methanol via asymmetric epoxidation

Chong, J. Michael; Wong, Susanna

doi:10.1021/jo00388a050

Cited by 26 publications

(5 citation statements)

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“…The hydroxyl group of chiral epoxy alcohol 10 was substituted by thioacetate in a one-pot reaction using triphenylphosphine (PPh 3 ), diisopropyl azodicarboxylate (DIAD), and thioacetic acid in tetrahydrofuran to give 11 in 96% yield (Scheme ) using a modified Mitsunobu procedure, developed by Volante . Treatment of 11 with sodium hydroxide (0.5 M) using standard conditions for the Payne rearrangement 20 failed to produce 12 , likely due to extensive polymerization of the terminal thiirane in the alkaline media .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

Brånalt¹,

Kvarnström²,

Classon³

et al. 1996

J. Org. Chem.

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The synthesis of [4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides is described. 2,3-Epoxy alcohol 10 was converted in one pot into thioacetate 11. Treatment of 11 under mild alkaline conditions gave thiirane 12 with inversion of configuration at C-2. We also found that thioacetate 11 rearranges into thiirane 14 under mild acidic conditions. This rearrangement reaction was shown by independent synthesis to proceed with net retention of configuration at C-2. We have proposed a tentative mechanism which may explain the results obtained. Opening of thiiranes 12 and 14 followed by deprotection gave (2R,3R)-2-thiothreitol (23) and (2S,3R)-2-thioerythritol (25), respectively. Regioselective silylation of the primary hydroxyl groups of 23 followed by treatment with trimethyl orthoformate gave 2-methoxy-1,3-oxathiolanes 26 and 27. Condensation with silylated bases followed by deprotection and separation of the anomers gave the oxathiolanylnucleosides. Compounds 29-31, 34, and 35 were found to be inactive when tested for inhibition of HIV-1 activity in vitro.

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Section: Resultsmentioning

confidence: 99%

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

Brånalt¹,

Kvarnström²,

Classon³

et al. 1996

J. Org. Chem.

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“…The tedious chromatographic separation required to remove the unwanted p -nitrobenzoate 6 from 5 prompted a search for an improved synthesis of 8 , and the epoxide 9 , obtained enantiopure after a single crystallization following Sharpless asymmetric epoxidation of the mono p -bromobenzyl ether of cis -buten-1,4-diol, provided the starting point for a new approach as shown in Scheme . Exposure of 9 to methylmagnesium bromide and cuprous iodide afforded a 3:1 mixture of 1,3- and 1,2-diols, from which the undesired 1,2-diol was easily removed by oxidative cleavage with sodium periodate.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Rhizoxin D, a Potent Antimitotic Agent from the Fungus Rhizopus chinensis

et al. 2002

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Rhizoxin D (2) was synthesized from four subunits, A, B, C, and D representing C3-C9, C10-C13, C14-C19, and C20-C27, respectively. Subunit A was prepared by cyclization of iodo acetal 21, which set the configuration at C5 of 2 through a stereoselective addition of the radical derived from dehalogenation of 21 at the beta carbon of the (Z)-alpha,beta-unsaturated ester. Aldehyde 29 was obtained from phenylthioacetal 24 and condensed with phosphorane 30, representing subunit B, in a Wittig reaction that gave the (E,E)-dienoate 31. This ester was converted to aldehyde 33 in preparation for coupling with subunit C. The latter in the form of methyl ketone 55 was obtained in six steps from propargyl alcohol. An aldol reaction of 33 with the enolate of 55 prepared with (+)-DIPCl gave the desired beta-hydroxy ketone 56 bearing a (13S)-configuration in a 17-20:1 ratio with its (13R)-diastereomer. After reduction to anti diol 57 and selective protection as TIPS ether 58, the C15 hydroxyl was esterified to give phosphonate 59. An intramolecular Wadsworth-Emmons reaction of aldehyde 62, derived from delta-lactone 60, furnished macrolactone 63, which was coupled in a Stille reaction with stannane 68 to give 2 after cleavage of the TIPS ether.

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“…In the course of a synthesis of oxetanocins A and G ( 1a,b ), the known epoxide (−)- 4 12 was made from the known monoprotected 2-butene-1,4-diol 3 (itself prepared by simple alkylation of butenediol in 88% yield) in 96% ee via a Sharpless epoxidation (Scheme 1). Addition of vinylmagnesium bromide proceeded highly stereoselectively to give primarily the 1,3-diol 5 , with a small inseparable impurity (presumably the 1,2-diol).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms¹

Jung

Nichols

1998

J. Org. Chem.

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We report a novel route to isonucleosides of the ‘methylene-expanded' oxetanocin class, in both the d- and l-enantiomeric forms, e.g., compounds l-(+)-2a, d-(−)-2a, and l-(−)-2b, beginning with the simple, known mono-p-bromobenzyl ether 3 of the very inexpensive 2-butene-1,4-diol. Sharpless asymmetric epoxidation of 3 gave either (−) or (+)-4 depending on the chirality of the tartrate used. The p-bromobenzyl ether was used since the epoxide product is crystalline and can be recrystallized to high optical purity. Opening of the epoxide with vinylmagnesium bromide gave the 1,3-diol 5, the primary alcohol of which was protected as the silyl ether 6. Treatment of 6 with iodonium bis(sym-collidine) perchlorate afforded the desired 5-(iodomethyl)tetrahydrofuran-3-ol 8 with loss of the bromobenzyl cation in the key step in the synthetic scheme. This iodide 8 was then converted into the bis(silyloxy)-protected alcohol 15 by acetylation to give the acetate 10, displacement of iodide with acetate, hydrolysis, and selective protection of the primary alcohols. The alcohol 6 could also be converted into 15 via initial acetylation and then iodocyclization to give 10. The diol 5 could also be converted into 15 by a similar route involving bis-acetylation and iodocyclization followed by functional group transformations. The tosylate of 15 was displaced with the anion of adenine or thymidine to give, after final desilylation, the desired isonucleosidesthe d-adenosine analogue (−)-2a and the l-adenosine and thymidine analogues (+)-2a and (−)-2b. All of the stereochemistry of the final products is derived from the first step of the synthesis, namely, the Sharpless asymmetric epoxidation of 3. The biological activity of the new compounds l-(+)-2a and l-(−)-2b against HIV was determined in the anti-HIV drug-testing system of the National Cancer Institute. The adenosine analogue l-(+)-2a was inactive in this screen, while the thymidine analogue l-(−)-2b showed moderate anti-HIV activity (IC50 > 2 × 10-4 M, EC50 = 8 × 10-7 M, TI50 > 250).

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Facile preparation of (2R,3S)- and (2S,3R)-3-[[(4-bromobenzyl)oxy]methyl]oxirane-2-methanol via asymmetric epoxidation

Cited by 26 publications

References 0 publications

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

Total Synthesis of Rhizoxin D, a Potent Antimitotic Agent from the Fungus Rhizopus chinensis

Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms¹

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Facile preparation of (2R,3S)- and (2S,3R)-3-[[(4-bromobenzyl)oxy]methyl]oxirane-2-methanol via asymmetric epoxidation

Cited by 26 publications

References 0 publications

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate1

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate1

Total Synthesis of Rhizoxin D, a Potent Antimitotic Agent from the Fungus Rhizopus chinensis

Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms1

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Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

Synthesis of Methylene-Expanded Oxetanocin Isonucleosides in Both Enantiomeric Forms¹