P-amino acid synthesis

The asymmetric Mannich reaction of an enolate and an imine furnishing valuable p amino carbonyls is a fundamental C C bond forming process in organic chemistry that has broad utility in organic synthesis particularly for P amino acid synthesis [1]. Extending the enolate component into a dienolate offers the opportunity for a bond forming event with an electrophile both at the a and the y positions of this ambident nucleophile (Scheme 5.1). 

Recently, we have demonstrated that 3 functions as an attractive chiral auxiliary for the synthesis of scalemic a-substituted carboxylic acids.22 In addition, we have extended the scope of the p-amino acid synthesis to include alkyl groups through a protected derivative of heterocycle 3.23 Thus, a unified approach to the synthesis of enantiomerically pure p-amino acids has been developed from 3. Recent efforts by Seebach, Juaristi, and co-workers24 on a saturated analog of 3 have developed routes to products substituted at C5 (a to the carbonyl). 

P-amino acids synthesis and activity against Candida albicans. Bioorg. Med. Chem. Lett., 13, 433-436. 

D A R A P S K I Amino Acid Synthesis (see Curtius) Amino acid synthesis from ethyl cyanoacetates... 

Amend, J. P. and Shock, E. L. (1998). Energetics of amino acid synthesis in hydrothermal ecosystems. Science 281,1659-1662. 

Answer The Strecker amino acid synthesis (p T 43) requires aldehyde (45) for which a 1,3-diX disconnection is appropriate. 

Decicco, C.P. and Grover, P. (1997) Asymmetric amino acid synthesis Mitsunobu reactions on chiral cyanohydrins. Synlett, 529-530. 

Studies of the intramolecular cyclization of P-amino acids have included the use of camphor-derived oxazoline A-oxide 66 and a [3+2] cycloaddition reaction as a step in the formation of the amino acid with the required stereochemistry <00OL1053, OOEJOC1595>. A diastereoselective synthesis of a ip-methylcarbapenem intermediate utilises a cyclization of a P-amino acid <99CC2365>. 

Synthesis of Enantiomerically Pure p-Amino Acid from 2-tert-Butyl-1-carbomethoxy-2,3-dihydro-4(1 H)-pyrimidinone (S)-p-Tyrosine-O-methyl Ether. 

Alternatively, the acidity of the aldehyde-derived CH or CH2 group can be enhanced by converting the isocyanide derived amide into an ester. According to this principle, tandem Ugi-Dieckmann was exploited in the context of carbapenem synthesis, where the first 4-membered ring was built through an intramolecular Ugi reaction of p-amino acid 66. Then, after a three-step manipulation of the carboxylic appendages, a Dieckmann cyclization afforded, stereoselectively, the desired carbapenem skeleton 67 [79]. 

Reduction of 3-nitroacrylates 43 by Saccharomyces carlshergensis Old Yellow Enzyme is the key step in the synthesis of optically pure P-2-amino acids (Scheme 2.18). High yields and enantioselectivities of the initially derived nitro-compounds 44 were achieved. The latter can be further chemically elaborated to the corresponding P-amino acids 45 [20]. 

The procedure described here has been used for the synthesis of further Boc-protected p-amino acids ... 

The approach of the alkylation of 5,6-diphenyltetrahydro-l,4-oxazin-2-one enolates (Equation 55) has the additional benefit that it could be extended to the synthesis of P-amino acids <2001JA3472> and y- or 5-amino acids <1998T10419>, as was shown in Scheme 22. 

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