Serine derivatives, synthesis

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

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... 

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... 

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. 

Scheme 4.17 Synthesis of serine-derived enantiomerically pure bromoallenes.

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. 

However, this strategy failed when applied to the synthesis of the cyclopeptide lissoclinamide 7. Here, the serine-derived oxazoline moiety could not be selectively thiolyzed in the presence of the threonine-derived oxazoline in the cyclopeptide 334. " The authors attributed this lack of chemoselectivity to the increased stability and thus reduced reactivity, of the serine-derived oxazoline in the macrocyclic scaffold. AU three oxazoline moieties reacted under the prolonged reaction conditions to give the trithio cyclopeptide 335 (Scheme 8.102). The structure of 335 was confirmed by conversion to the tristhiazoline cyclopeptide 336. 

DIASTEREOSELECTIVE SYNTHESIS OF PROTECTED VICINAL AMINO ALCOHOLS (S)-2-[(4S)-N-TERT-BUTOXYCARBONYL-2.2-DIMETHYL-1,3-OXAZOLIDINYL1-2-TERT-BUTYLDIMETHYLSILOXYETHANAL FROM A SERINE-DERIVED ALDEHYDE. 

Fig. 15 The first chemical synthesis of 64, which involves the condensation of three serine derivatives (86) with subsequent cyclization and addition of DHB groups...

Formamidines also activate secondary centres towards lithiation, and have been used extensively in the synthesis of the benzylisoquinolines, where the lithiation takes place at a benzylic position. Formamidines bearing chiral substituents (for example the serine-derived 85) allow the introduction of asymmetry at such centres.58... 

S-Hydroxy-l-azetidinones. A biomimetic synthesis of the y3-lactam 4 from BOC-L-serine (1) has been reported. The protected serine derivative is converted into the hydroxamic acid 2 by condensation with O-benzylhydroxylamine mediated by the water-soluble l-ethyl-3(3 -dimethylaminopropyl)carbodiimide (1, 371). The product is cyclized directly in high yield to the / -lactam 3 by treatment with diethyl azodicarboxylate and triphenylphosphine. No racemization is observed. Deprotection by catalytic hydrogenation gives the N-hydroxy-jS-lactam 4. Previous biomimetic syntheses of 2-azetidinones have involved cyclization ot /3-cMoroamides with sodium hydride (e.g., 7, 335). 

A method for the enantioselective synthesis of the ftmctionalised carbapenam core 38 from D-serine-derived pyrrolidines has been reported <03JOC187>. Disubstituted pyrrolidines, obtained from the retro Dieckmann reaction of azabicyclo[2.2.1]heptan-2-one-1-carboxylic acid methyl esters, have been used as starting materials to develop concise syntheses of all four stereoisomers of carbapenam-3-carboxylic acid methyl esters <03JOC2889>. The synthesis of 1-methylcarbapenams 39 by intramolecular attack of lactam nitrogen on a 77 -propargylpalladium complex has been reported <03JOC8068>. 

Scheme 8) are employed for the introduction of nitrogen alkylation into a peptide chain in order to suppress aggregation that interferes with chain assembly. Pentafluorophenyl esters of Fmoc-cysteine derivatives are employed in solid-phase synthesis to circumvent the enantiomerization that occurs during certain onium salt mediated couplings of the corresponding acids which have to be carried out in the presence of tertiary amines. The same phenomenon may apply to serine derivatives. Water-soluble tetrafluoro-4-sulfophenyl esters 22 are available. ... 

An elegant total synthesis of the semiprotected form of lincosamine was realized by Marshall and Beaudoin [116]. An aldehyde derived from destomic acid (6-amino-6-deoxy-L-g/yc ro-D-ga/acto-heptonic acid) was derived in a similar way from a L-serinal derivative via hetero Diels-Alder addition to 1-ethoxy-3-[(trimethylsilyl)oxy]-4-benzyloxy-1,3-butadiene [142]. A similar method was applied to the preparation of a semiprotected form of anhydrogalantinic acid, a component of the antibiotic galantin I [142]. 

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