Didehydroamino acids

TABLE 7.32. SYNTHESIS OF UNSATURATED 5(4/T)-OXAZOLONES VIA CYCLIZATION OF a,P-DIDEHYDROAMINO ACIDS OR a,P-UNSATURATED CARBODIIMIDES... 

Deprotection of the a,p-didehydroamino acid 803 with TEA unexpectedly afforded the TEA salt of the 5(4//)-oxazolone 804 via an intramolecular cyclization (Scheme 7.246). °"... 

As discussed in Section 11.1.1.2.3 most of the aliphatic DHAs such as AAla, AVal, ALeu, Alle, AAsp, AGlu, and AOrn have been prepared either by (3-elimination, N-chlorination/ dehydrochlorination, or from Af-carboxy a, 3-didehydroamino acid anhydrides which, in turn, are prepared by condensation of an a-oxo acid with benzyl carbamate. 

V-Carboxy- ,p-didehydroamino acid anhydrides 76 have been employed with success in the synthesis of peptides177-83 (Scheme 25). The ANCA formed from the reaction of (Z)-DHAwith thionyl chloride does not form the desired peptides on direct opening with amines... 

For the synthesis of optically pure building blocks we mainly focused on the synthesis of protected noncoded (R)- and (S)-amino acids, as they can be synthesized reliably in enantiomerically pure form with a large variety of side chains using asymmetric hydrogenation of a-amino-a, 3-didehydroamino acids using cationic diphosphine rhodium catalysts.216,217 As a typical example of a reactophore we present a-alkynyl ketones, which is a representative bis-acceptor molecule. In Scheme 5 are depicted some of the many synthetic applications of acetylenic ketones in heterocyclic synthesis, which have great potential for combinatorial and parallel organic synthesis. 

Didehydroamino acids, R CH=C(NH2)COOR2.7 Review.8 Aryl didehy-droamino acids (R1 = Ar) can be prepared by a modified Heck coupling of N-protected 2-amidoacrylates with aryl iodides catalyzed by Pd(OAc)2 under phase-transfer conditions, which results in the (Z)-didehydroamino acid in moderate to good yield (32-80%). This reaction is particularly useful for preparation of O-benzyl, N-Boc-protected aryl didehydroamino acids. 

The ethyl aluminum dichloride-catalyzed Michael alkylations of some indoles with N-(diphcnylmethylcnc)-a,()-didehydroamino acid esters allowed successful short synthesis of the tryptophan derivative and the 1,1-diphenyl-p-carboline derivatives, as well as compounds 253 and 252 (Scheme 55) [ 178]. 

Also, solid phase synthesis of peptides containing o, )3-didehydroamino acids are common. In this case the carbodiimide affects dehydration to generate the a,)8-didehydroamino acids 686. Eor example, the water soluble carbodiimide EDC hydrochloride (EDCCl) is used in this dehydration reaction, also using CuCl as catalyst. ... 

This review articie provides an introduction to foided and extended conformationai motifs of synthetic peptidomimetics as tempiates for chemicai bioiogy appiications. Severai variants of these 3-dimensionai structures have been assessed, which comprise versatiie scaffoids for presentation of side-chain and main-chain peptide groups for moiecuiar recognition. Specificaiiy, reievant parameters and stereochemicai consequences are discussed for heiices of peptidomimetics based on 1) a-amino acids alkylated (e.g., methylated or ethylated) at the C"-atom 2) a,P-didehydroamino acids, in particular a,P-didehydrophenylalanine, with a carbon-carbon double bond between the a- and fS-positions 3)... 

Alkylidene- and 4-arylidene-5(4/0-oxazolones, which are versatile intermediates for the synthesis of didehydroamino acids, offer another site, Ca, for reaction. The propensity for nucleophiles to attack at this position has been exploited in the synthesis of other heterocycles. A -Acyldithio-carbamic acids add in Michael fashion, and the intermediates undergo cyclization with concomitant oxazolone ring opening to furnish 2-thioxo-l,3-thiazin-4-ones (87) (Scheme 27) <92S919>. 

Cyclopropanation. Unsaturated amidt lam are found to undergo Pd(II)-catalyzed c tonyl group. For the access of 1-aminocyclc a./3-didehydroamino acid derivatives with d... 

Schmidt, U., Griesser, H., Leitenberger, V. et al. (1992) Amino-acids and peptides. 81. Diastereoselective formation of (Z)-didehydroamino acid-esters. Synthesis, 487 90 Burk, M.J., Gross, M.F. and Martinez, J.P (1995) As3fmmetric catalytic synthesis of P-branched amino acids via highly enantioselective hydrogenation of a-enamides. Journal of the American Chemical Society, 117, 9375-9376. 

Carlstrom, A.S. and Frejd, T. (1989) Palladium-catal3raed s3mthesis of didehydroamino acid derivatives. Synthesis, 414-8. 

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