A new enantioselective synthesis of β-amino acids

Saylik, Dilek; Campi, Eva M.; Donohue, Andrew C.; Jackson, W. Roy; Robinson, Andrea J.

doi:10.1016/s0957-4166(01)00097-0

Cited by 44 publications

(28 citation statements)

References 24 publications

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“…The enantioselectivities were poor in both cases. These results were consistent with those reported for the hydrogenation of ␣-phthalimidomethyl-␤-methylacrylate, which gave only 10% ee (67).…”

supporting

confidence: 92%

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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supporting

confidence: 92%

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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“…Scheme 3, above). This approach has been investigated by Jackson and co-workers 190 in pursuing the enantioselective hydrogenation of ␣,␤-unsaturated nitrile and methyl ester derivatives (Scheme 27). The corresponding nitriles can be pre- 14 The high regioselectivity observed in the enolate generation of acyloxazolidinones that also contain an ester group must be attributed to the increased acidity (or deprotonation rate) of the ␣-hydrogen adjacent to the imide over the ester group.…”

Section: -Amino Acids By Transition-metal Catalyzed Reactionsmentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

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Although they are less abundant than their alpha-analogues, beta-amino acids occur in nature both in free form and bound to peptides. Oligomers composed exclusively of beta-amino acids (so-called beta-peptides) might be the most thoroughly investigated peptidomimetics. Beside the facts that they are stable to metabolism, exhibit slow microbial degradation, and are inherently stable to proteases and peptidases, they fold into well-ordered secondary structures consisting of helices, turns, and sheets. In this respect, the most intriguing effects have been observed when beta2-amino acids are present in the beta-peptide backbone. This review gives an overview of the occurrence and importance of beta2-amino acids in nature, placing emphasis on the metabolic pathways of beta-aminoisobutyric acid (beta-Aib) and the appearance of beta2-amino acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of the syntheses of both achiral and chiral beta2-amino acids is presented. While there are numerous routes to achiral beta2-amino acids, their EPC synthesis is currently the subject of many investigations. These include the diastereoselective alkylation and Mannich-type reactions of cyclic- or acyclic beta-homoglycine derivatives containing chiral auxiliaries, the Curtius degradation, the employment of transition-metal catalyzed reactions such as enantioselective hydrogenations, reductions, C-H insertions, and Michael-type additions, and the resolution of rac. beta2-amino acids, as well as several miscellaneous methods. In the last part of the review, the importance of beta2-amino acids in the formation of beta-peptide secondary structures is discussed.

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“…The conjugate 1,4-addition (Michael-type reaction) of chiral N-nucleophiles to 2substituted acrylates, followed by diastereoselective protonation, is yet another method for their preparation, in which bonds 2 and 4 are formed [35 ± 38]. Finally, chiral metal complexes have permitted the isolation of enantiomerically enriched b 2 -amino acids by construction of the 1 4 [39], 4 5 [40], or 4 7 bonds [41], albeit often with low enantioselectivities and, in any case, applied only for derivatives with alkyl or aryl side chains.…”

mentioning

confidence: 99%

Enantioselective Preparation of β²‐Amino Acids with Aspartate, Glutamate, Asparagine, and Glutamine Side Chains

Lelais

Campo

Kopp

et al. 2004

Helvetica Chimica Acta

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S)-b 2 -Homoamino acids with the side chains of Asp, Glu, Asn, and Gln have been prepared and suitably protected (N-Fmoc, CO 2 t Bu, CONHTrt) for solid-phase peptide syntheses. The key steps of the syntheses are: N-acylation of 5,5-diphenyl-4-isopropyl-1,3-oxazolidin-2-one (DIOZ) with succinic and glutaric anhydrides (Scheme 2), alkylation of the corresponding Li-enolates with benzyl iodoacetate and Curtius degradation (Scheme 4), and removal of the chiral auxiliary (Scheme 5). In addition, numerous functional-group manipulations (CO 2 H > CO 2 t Bu, CO 2 Bn > CO 2 H, CbzNH 3 FmocNH, CO 2 H 3 CO 2 NH 2 3 CONHTrt; Schemes 2, 4, 5, and 6) were necessary, in order to arrive at the four target structures. The configurational assignments were confirmed by X-ray crystal-structure determinations (Scheme 2 and Fig. 3). The enantiomeric purities of a b 2 hAsn and of a b 2 hGln derivative were determined by HPLC on a Chiralcel column to be 99.7 : 0.3 and > 99 : 1, respectively (Fig. 4). Notably, it took up to twelve steps to prepare a suitably protected trifunctional product with a single stereogenic center (overall yield of 10% from DIOZ and succinic anhydride)! Part of the Master Thesis (Diplomarbeit) of S. K., ETH-Z¸rich, 2003. 5 ) With the exceptions of Fmoc-b 3 hHis(Trt)-OH and Fmoc-b 3 hCys(Trt)-OH, all −proteinogenic× b 3 -amino acids, which can be prepared by ArndtÀEistert homologation of the corresponding a-amino acids, are commercially available.compounds for their use in solid-phase b-peptide synthesis is the Fmoc protection of the b-amino group, and the t Bu or Trt protecting group on the side chains. Thus, we thought that 3-acyl-DIOZ derivatives of succinic and glutaric acids could serve as precursors for the corresponding b 2 -homoaspartic and b 2 -homoglutamic acids, respectively. The amino functionality would be introduced either by a diastereoselectiveMannich-type reaction (cf. bond 1 in Fig. 1) or by a carbalkoxymethylation, followed by Curtius degradation (connections 1 2 in Fig. 1), to give the desired amino acid skeleton, which could be further elaborated by protecting-group exchange (Scheme 1). Scheme 1. Retrosynthetic Analysis for the Preparation of the b 2 -Amino Acids with Asx and Glx Side ChainsHelvetica Chimica Acta ± Vol. 87 (2004) 1547 Fig. 2. Target b 2 -amino acid derivatives Scheme 2. Nucleophilic Ring Opening of the Succinic and Glutaric Anhydrides ( 3 1 and 2), N-Acylation of (R)-DIOZ to Form the Acyloxazolidinones 3 and 4, Respectively, and X-Ray-Crystal Structure of 3Helvetica Chimica Acta ± Vol. 87 (2004) 1548 7 ) The reaction was rather messy and the formation of polymerization products were observed.

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A new enantioselective synthesis of β-amino acids

Cited by 44 publications

References 24 publications

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

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

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

Enantioselective Preparation of β²‐Amino Acids with Aspartate, Glutamate, Asparagine, and Glutamine Side Chains

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A new enantioselective synthesis of β-amino acids

Cited by 44 publications

References 24 publications

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

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

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

Enantioselective Preparation of β2‐Amino Acids with Aspartate, Glutamate, Asparagine, and Glutamine Side Chains

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Product

Resources

About

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

Enantioselective Preparation of β²‐Amino Acids with Aspartate, Glutamate, Asparagine, and Glutamine Side Chains