An enantiospecific synthesis of β-amino acids

Jefford, C. W.; Wang, Jianbo

doi:10.1016/s0040-4039(00)77503-4

Cited by 48 publications

(9 citation statements)

References 24 publications

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“…Compound 3 or its open chain analogues b-amino-g-hydroxy carboxylates are active components of many biologically active natural products, such as antifungal/antibiotic peptides [16] and antimalarial alkaloids, [17] as well as active pharmaceuticals, such as gastroprotective drugs [18] and inhibitors of phosphodiesterase [19] and HIV-1 protease. [20] Apart from being associated with biological as well as pharmaceutical activities, this structural subunit is also used in preparing functionalized b-amino acids, [21] oxazolidinones, [22] and aziridines. [23] Generally, this substructure is synthesized either from d-aspartic acid [24] or from b-amino alcohols by using multiple steps.…”

Section: Resultsmentioning

confidence: 99%

Dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate as a Designer Substrate in the Syntheses of Important Heterocyclic Scaffolds

2012

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Section: Resultsmentioning

confidence: 99%

Dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate as a Designer Substrate in the Syntheses of Important Heterocyclic Scaffolds

2012

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“…The required iodide 2 may be obtained by iodotrimethylsilanemediated ring opening of the lactone 3 and quenching of the resultant silyl ester with an alcohol. 15,16 Alkylation of the lactone 4 (itself derived from manipulation of L-aspartic acid) would give the precursor to the ring-opening reaction 3. The appropriate choice of nitrogen protecting group is important since it must tolerate the conditions used for the iodotrimethylsilane ring opening in addition to being compatible with organozinc chemistry.…”

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confidence: 99%

“…A sulfonamide protecting group was then considered as it is known to tolerate these conditions. 15,16 Although we were able to synthesise the required alkyl iodide 2 (R = H, PG = Ts), reaction of this iodide with zinc resulted in recovery of large amounts of 4-methylphenylsulfonamide, arising from decomposition of the presumed organozinc reagent by b-elimination. Although we had previously shown that use of the strongly electron-withdrawing TFA group resulted in stabilisation of b-amino organozinc reagents (by suppressing internal coordination of the carbonyl group to zinc, and thereby changing the mechanism of the elimination), 12 use of the even more electron-withdrawing tosyl group presumably allows a faster elimination process.…”

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confidence: 99%

An Approach to the Synthesis of anti-β²,³-Amino Acids: Application of β-Trifluoroacetamidoorganozinc Reagents

Bartrum¹,

Jackson²

2009

Synlett

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An approach to the synthesis of anti-b 2,3 -amino acids is reported. The key steps involve stereoselective lactone alkylation followed by ring opening with iodotrimethylsilane/ethanol to give iodo esters. Formation of the organozinc reagents from these iodo esters, followed by either Pd-or Cu-catalysed reaction with electrophiles gives protected b 2,3 -amino acids. The trans stereochemistry in the enolate alkylation is confirmed for the allylated anti-lactone by X-ray crystallography.

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“…The synthesis of enantiopure ␤-amino acids has been extensively studied (6)(7)(8)(9). However, the known methods are mostly for the synthesis of ␤-substituted ␤-amino acids, and their preparation still suffers from a long synthetic sequence, low product yields, and laborious execution (10)(11)(12)(13)(14). For example, a recently reported synthesis of 1a involved nine steps from 3-phenylpropanoic acid (15)(16)(17)(18).…”

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confidence: 99%

Enantioselective hydrogenation of α-aminomethylacrylates containing a free NH group for the synthesis of β-amino acid derivatives

Qiu

Prashad

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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We describe highly enantioselective synthesis of ␤-amino acid derivatives (1a-c) using asymmetric hydrogenation of ␣-aminomethylacrylates (2a-c), which contain a free basic NOH group, as the key step. The ␣-aminomethylacrylates (2a-c) were prepared using the BaylisHillman reaction of an appropriate aldehyde with methyl acrylate followed by acetylation of the resulting allylic alcohols (4a-b) and S N2 -type amination of the allylic acetates (3a-b).asymmetric catalysis ͉ Baylis-Hillman reaction I n recent years, ␤-amino acids have received increasing attention as constituents of molecules with interesting biological and pharmacological activities (1-5) such as hypoglycemic and ketogenic activities. They are key moieties of a number of bioactive molecules, such as in taxol and in peptidic natural products with various enzyme inhibiting activities. Nonpeptidic ␤-amino acids are found in well known ␤-lactams. Considering their importance, asymmetric synthesis of enantiomerically pure ␤-amino acids has become an important challenge for organic chemists. The synthesis of enantiopure ␤-amino acids has been extensively studied (6-9). However, the known methods are mostly for the synthesis of ␤-substituted ␤-amino acids, and their preparation still suffers from a long synthetic sequence, low product yields, and laborious execution (10-14). For example, a recently reported synthesis of 1a involved nine steps from 3-phenylpropanoic acid (15-18). Peptide deformylase (PDF, EC 3.5.1.31), a metallopeptidase found in prokaryotic organisms, is essentially required for bacterial growth (19)(20)(21). Certain N-formyl hydroxylamine compounds were recently revealed to have good antibacterial function by means of their PDF-inhibiting capabilities. Chiral compounds 1, ␣-substituted ␤-amino acid derivatives, are key intermediates in the synthesis of this kind of compounds (15)(16)(17)(18)22). Their prochiral dehydroprecursors 2 could be prepared in high yields via a synthetic process shown in Scheme 1. Asymmetric hydrogenation of these substrates 2 is the simplest and most direct route to synthesize 1 because of its inherent efficiency and atom economy. In contrast to the great progress in the synthesis of ␤-substituted ␤-amino acids and derivatives via enantioselective hydrogenations (23-38), reports on the synthesis of ␣-substituted ␤-amino acids with this protocol are very limited. To the best of our knowledge, only one exceptional example has been given, very recently by Zheng and coworkers (38), using Rh-monophosphorus catalyst system for the hydrogenation of ␤-phthalimide acrylates. However, the activity of the catalyst was not high, and only E-isomers of substituted ␤-phthalimide acrylates were investigated. In fact, compounds 2 were a mixture of E-and Z-isomers formed in the synthesis, and they were not always easy to separate into single isomers. Generally, it is also difficult to achieve high activity and enantioselectivity for the system containing both isomers (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). In light of the suc...

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An enantiospecific synthesis of β-amino acids

Cited by 48 publications

References 24 publications

Dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate as a Designer Substrate in the Syntheses of Important Heterocyclic Scaffolds

Dimethyl [(2R,3R,5S)‐5‐phenylmorpholine‐2,3‐diyl]diacetate as a Designer Substrate in the Syntheses of Important Heterocyclic Scaffolds

An Approach to the Synthesis of anti-β²,³-Amino Acids: Application of β-Trifluoroacetamidoorganozinc Reagents

Enantioselective hydrogenation of α-aminomethylacrylates containing a free NH group for the synthesis of β-amino acid derivatives

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