L-Isoserine

The use of lipase-catalyzed ester hydrolyses or transesterification reactions has led, interestingly, to an efficient method for synthesizing the N-benzoyl-(21 ,3S)-3-phenyl isoserine moiety, the C-13 side chain of taxol. The Mucor miehei lipase proved to be uniquely suited for the stereospecific transesterification of racemic methyl fra s-/l-phenyl glycidate. Further improvement of this reaction led to the choice of an isobutanol-hexane mixture (1 1 vol/vol) as the... 

L-j -Malamidic acid (16) is the penultimate intermediate in the synthesis of (5)-isoserine (17), an amino acid component of several biologically active peptides. Treatment of 16 with sodium hypochlorite in alkaline solution produces 17 (28% yield) via a Hofmann rearrangement [23]. 

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

AIB aminoisobutyric acid DAB (x,y-diaminobutyric acid DAP diaminopropionic acid DHA 2,6-diamino-7-hydroxyazelaic acid HIV D-2-hydroxyisovaleric acid ISER isoserine LAC L-lactic acid MO A 6-methyloctane acid (isopelargonic acid) MVAL iV-methyl-L-valine SP spermidine BTYR / -tyrosine mod, modified... 

Isoserine (l-Hydroxy-2.aminopropionic acid, l-hydroxy. -alanine, 2 amindlaotic acid) H2N-CH2-CH(0H)-C00H C3H7O3N MW, 105... 

KOCl, KOH), and cyclobutylamine hydrochloride (PhI(02CCF3)2) published in Organic Syntheses, and 3-nitroaniline (NaOCl, NaOH) published as an undergraduate laboratory experiment, The reader is also referred to these syntheses reported in Organic Reactions Neopentylamine (Br2, NaOH), -pentadecylcarbamate (Br2, NaOMe), 2-methyl-l,4-diaminobutane (Bri, NaOH), (5)-isoserine (Br2, Ba(OH)2), y-truxillamic acid (NaOCl, NaOH), 3-bromoaniline (Br2, KOH), and phenylacetaldehyde (NaOCl, NaOH) (from cinnanamide). 

Examples 1 to 5 in Table 1.1 illustrate simple displacement of a bromide (reactions 1 and 4) or a chloride (reactions 2,3, and 5). Reaction 1 illustrates a radical chain extension reaction that reacts ethylene and methyl bromoacetate 1.17), with AIBN (flzofeis-isobutyronitrile) as a catalyst, to produce the requisite bromo-cster. The reaction is not very selective, however, since it produced a mixture of 1.18 and 1.19. The reaction was not very selective and the observed products arose from addition of one and two equivalents of ethylene, respectively, to 1.17. Subsequent treatment with ammonia, the key reaction for this section, led to a mixture of 4-aminobutanoic acid and 6-aminohexanoic acid, 1.2 and 1.4. In reaction 2, ethyl 4,4,4-trifluoropropanoate (J.20) reacted with PCI3 and bromine to give ethyl 3-bromo-4,4,4-trifluorobutanoate, which reacted with ammonia to give 3-amino-4,4,4-trifluorobutanamide, 1.21. Reaction 3 shows the reaction of P-halo lactic acid (3-chloro-2-hydroxypropanoic acid, 1.22) with 28% aqueous ammonia, in an autoclave, to give isoserine (3-amino-2-hydroxypropanoic acid, 1.23). Both halo-acids l and halo-esters 2 have been converted into hydroxy amino acids typical products are 3-... 

A closely related chiral template is L-P-malamidic acid 5.182), which was converted to 5.183 using a hypervalent iodine species. Acid hydrolysis gave S-isoserine (3-amino-2-hydroxypropanoic acid, 5.35). 

Z. Guo, T. Shi, J. Jiang, L. Yang, W. Hu, Org. Biomol. Chem. 2009, 7, 5028-5033. Component match in rhodium catalyzed three-component reactions of ethyl diazoacetate, H O and aryl imines a highly diastereoselective one-step synthesis of 3-aryl isoserine derivatives. 

This approach is also quite common in the recent literature. For example, Majewski and Palyam presented a useful organocatalytic approach to derivatives of DNJ, based on the reaction of dioxanone 48 with (5")-isoserinal hydrate 49 catalyzed by (S)-proline. This process led to linear ketone 50 which was converted into N-isopropyl-L-ido-DNJ 51 (Scheme 9). 

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