Serine derivative

Amino acid synthesis from aldehydes and hydantoin (Bergmann), synthesis of serine derivatives (Erlenmeyer) or of y-hydroxyaminoacids (Plochl)... 

In a study of the deprotection of the MEM ethers of hydroxyproline and serine derivatives, it was found that the MEM group was stable to conditions that normally cleave the t-butyl and BOC groups [CF3COOH, CH2CI2, 1 1 (v v)]. The MEM group was also stable to 0.2 N HCl, but not stable to 2.0 N HCl or HBr-AcOH. ... 

The cyclohexyl phosphate, used in the protection of phosphorylated serine derivatives, is introduced by the phosphoramidite method and cleaved with TFMSA/MTB/m-cresol/l,2-ethanedithiol/TFA, 4 h, 0° to rt. " ... 

With Oxygen Nucleophiles Aziridine ring-opening of 111 (Scheme 3.42) with water in the presence of a catalytic amount of TsOH gave the corresponding (3-hydrox-yphenylalanine derivative 121 in 72% yield as the major isomer [74], Treatment of N-(p-tolylsulfmyl) aziridine-2-carboxylates with TFA and subsequent aqueous workup resulted in the formation of j3-substituted serine derivatives [62, 63, 101]. Under these reaction conditions, not only was the aziridine ring opened, but also the N-sulfmyl group was removed treatment of 122 (Scheme 3.43) with TFA at 73 °C, for example, afforded 123 in 75% yield [101],... 

The related serine derived (4S)-4-methoxycarbonyl-3-(l-oxopropyl)-2-thiono-l,3-oxazolidine 11, and the cysteine derived (4A)-4-methoxycarbonyl-3-(l-oxobntyl)-2-thiono-1,3-thiazolidine 13, also serve as efficient chiral auxiliaries in boron- and tin(II)-mediated aldol condensations98. Thus, conversion of 11 into the boron or tin enolate, followed by reaction with 2-methylpropanal affords predominantly one adduct. Subsequent methanolysis and chromatographic purification delivers the syu-methyl ester in 98% ee. 

Via these optimized routes, the N-protected pyrimidine nucleoamino acids 6 and 9 were synthesized very efficiently in three high-yielding steps, starting from an inexpensive and commercially available serine derivative. The common intermediate O-MTM ether 3 can be synthesized on a multigram scale and is stable for years if stored in a refrigerator. 

On the other hand, following the same sequences from the differently protected serine-derived nitrone 168, through the formation of hydroxylamines 169, C2 epimers of carboxylic acid and aldehydes are obtained, i.e., (2S,3R)-170 and (2S,3R)-171. Moreover, the syn adducts 164 were exclusively obtained in the addition of Grignard reagents to the nitrone 163, whereas the same reactions on nitrone 168 occurred with a partial loss of diastereoselectivity [80]. Q, j6-Diamino acids (2R,3S)- and (2R,3R)-167 can also be prepared from the a-amino hydroxylamines 164 and 169 by reduction, deprotection and oxidation steps. The diastereoselective addition of acetylide anion to N,N-dibenzyl L-serine phenyhmine has been also described [81]. 

C-N.m.r. Chemical-shift Data for Various a- and /J-D-Glycosyl-L-serine Derivatives... 

In a synthesis of the L-serine derivative 133, Kunz and Buchholz100 treated N-(benzyloxycarbonyl)-L-serine 2-bromoethyl ester (135) with tetra-O-benzoyl-a-D-glucopyranosyl bromide (136) protection of the... 

Phenols were constructed form novel serine-derived handle 51, which was stable to acids (TFA) and bases (pyridine) (Scheme 21) [60]. The final products were released from the support by fluoride ion. 

An alternative procedure for the synthesis of aliphatic 2-substituted oxazoline hydroxamates was described by Pirrung and colleagues in the context of preparing inhibitors of E. coli LpxC zinc amidase [378], As shown in Scheme 6.210 a, the protocol involved the cyclization of suitable amides, formed in situ by acylation of a serine-derived 0-2,4-dimethoxybenzyl (DMB)-protected hydroxamate. The cyclization... 

To carry out 1,3-dipolar cycloadditions with alkyl acrylates, nitrones of various structures such as ferrocenylnitrones (141), nitrones derived from chiral amino acids (210), L-serine-derived nitrones (660) and N -substituted C -phosphorylated nitrones (263) have been used. 

The Michael addition reaction of the serine-derived oxazolidine 326 with ethyl acrylate gave two products. The major product of the reaction was found to be the bicyclic compound 327, which was formed in 27% yield, accompanied by the unsaturated ester 328. The Dess-Martin oxidation of 327 resulted only in formation of the elimination product, the 7,7a-dihydro-177, 377-pyrrolo[l,2-r ]oxazole 328 (Scheme 46) <2001JOC7555>. 

The solid-phase synthesis of glycopeptides was first realized by applying the polymeric benzyl ester principle of Merrifield. According to this methodology, Lavielle and associates (50) used 7V-(tm-butyloxycarbonyl)-<9-glycosyl serine derivative 153 for condensation with resin-linked alanine 154. 

Likewise, the galactosylation of O-glycopeptide derivatives 189-191 to give O-lactosamine - L-serine derivatives (192-194) using (1 - 4)-/ -d-... 

Scheme 4.17 Synthesis of serine-derived enantiomerically pure bromoallenes.

Use of nonenantiopure amino acid derivatives as starting materials. Notable examples have been serine derivatives that isomerized during tert-butylation and glutamate that isomerized during cyclodehydration to pyro-glutamate. 

On the other hand, in contrast with the non-Kolbe reaction of (113), that of L-serine derivative (115) gave an optically active a-methoxylated product (116) with 39% ee when graphite was used as the anode... 

Fig. 45 Stereoselective methoxylation of serine derivatives by anodic decarboxylation [223].

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Experimental Procedure 4.2.4. Etherification of a Serine Derivative by Intermo-lecular O-H Insertion Methyl (25)-3-[(Ethoxycarbonyl)methoxy]-2-(benzyloxy-carbonylamino)propanoate... 

D1methylethyl (S)- or (R)-4-Formyl-2,2-dimethy1-3-oxazolidinecarboxylate A Useful Serinal Derivative P. Garner and J. M. Park, Department of Chemistry,... 

Thus, a new and convenient procedure has been developed by Defrancq and coworkers for the synthesis of 3 -ohgonucleotide conjugates 83 through the formation of glyoxyhc oxime bonds (Scheme 44). This has been achieved by using a novel sohd support 82 for ODN synthesis. Support 82 was conveniently prepared from a commercially available serine derivative in a few steps. The glyoxylic oxime bonds showed higher stability than aldoxime bonds at acidic to neutral pH but lower stabihty at alkaline pH. 

Hoechst has reported an enantioselective approach toward the key azabicyclo[3.3.0] octane-3-carboxylic acid 46 that preserves the stereochemistry of the L-serine-derived starting material (Urbach and Henning, 1991). L-Serine methyl ester (48) was alkylated... 

An alternative and elegant approach to bicyclo[3.3.0]isoxazolidines from alkenyl oximes was developed by Grigg (205) and applied in asymmetric reactions by Hassner et al. (206-209) and others (210). The optically active L-serine derived oxime 130 was proposed to be in a thermal tautomeric equilibrium with the nitrone tautomer 131, which underwent an intramolecular 1,3-dipolar cycloaddition to form the product 132 in 80% yield as a single stereoisomer (Scheme 12.44) (209). 

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