Amino acid synthesis methylation

Oxazol-5(2H)-one, 2-benzylidene-4-methyl-tautomerism, 6, 186 Oxazol-5(2ff)-one, 2-methylene-isomerization, 6, 226 Oxazol-5(2H)-one, 2-trifluoromethyl-acylation, 6, 201 Oxazol-5(4ff)-one, 4-allyl-thermal rearrangements, 6, 199 Oxazol-5(4H)-one, 4(arylmethylene)-Friedel-Crafts reactions, 6, 205 geometrical isomerism, 6, 185 Oxazol-5(4ff)-one, 4-benzylidene-2-phenyl-configuration, 6, 185 photorearrangement, 6, 201 Oxazol-5(4ff)-one, 4-benzyl-2-methyl-Friedel-Crafts reactions, 6, 205 Oxazol-5(4ff)-one, 4-methylene-in amino acid synthesis, 6, 203 Oxazol-5(4ff) -one. 2-trifluoromethyl-hydrolysis, 6, 206 Oxazolones... 

In the search of new methodologies for the asymmetric synthesis of nonproteinogenic amino acids, 8-methyl-4,8a-diphenyltetrahydro-17/-pyrrolo[2.1 -r l, 4 oxazinc-l, 6(7//)-dionc 62, obtained as described in Scheme 24 (Section 11.11.7.3), was selectively reduced at the lactam carbonyl with BH3 and further opened by hydrogenolysis to give syn-disubstituted proline derivative 64 in 95% yield <1997SL935> (Scheme 6). It is noteworthy that hydrogenolysis did not affect the benzylic position of bicyclic compound 63. 

There are several commercially available sulfonylurea herbicides that contain a 2-pyrimidine group <2006H(68)561>. These compounds, which function by inhibition of acetolactate synthase (ALS), an enzyme involved in the early stage of branched-chain amino acid synthesis, include sulfometuron-methyl 1095, primisulfuron-methyl 1096, chlorimuron-ethyl 1097, bensulfuron-methyl 1098, ethoxysulfuron 1099, nicosulfuron 1100, and pyrazosulfuron-ethyl 1101. Related nonsulfonylureas include the sulfide pyrftalid 1102 and the ether pyriminobac-methyl 1103. 

The use of mixed anhydrides derived from Al-acyl-a-amino acids has become an interesting strategy for synthesis of saturated 5(4//)-oxazolones 101 (Scheme 7.26). For example, reaction of Al-acyl-a-amino acids with methyl chloroformate in the presence of Al-methylmorpholine affords racemic 5(47/)-oxazolones. 

Asymmetric amino-acid synthesis.1 The (S)-l-f-butyl 4-methyl N-benzyloxy-carbonylaspartate (1), prepared in 80% yield from the 4-methyl ester of aspartic acid, undergoes diastereoselective alkylation at the -carbon (LDA or lithium hexa-... 

In solution, phase amino acid derived methyl ester N-Fmoc-Tyr-OMe 4 was successfully condensed under Mitsunobu conditions with 2,3,4,6-tetra-Oacetyl-D-glucose 2 to afford the fully protected glucosylamine 5. The reaction provides products of analytical purity and predictable stero-chemistry, as confirmed by H/ C NMR. Synthetic conditions and protective groups for glycopeptides synthesis have been investigated. Mitsunobu conditions employed in solution phase are based on the improved redox system l,l -azodicarbonyldipiperidine (ADDP)—tributylphosphine (TBP) in... 

Scheme 8.3 Synthesis of a-amino acids from methyl ketones.

The D(R) isomer of the amino acid A-methyl-D-aspartate, more commonly known as NMDA serves as the endogenous agonist at a number of central nervous system (CNS) receptor sites. This agent is not only involved in neurotransmission, but also modulates responses elicited by other neurochemicals. A relatively simple peptide-like molecule has been found to act as an antagonist at NMDA receptors. This activity is manifested in vivo as antiepdeptic activity. This agent in addition blocks the nerve pain suffered by many diabetics, which is often called neuropathic pain. The synthesis begins by protecting the unnatural D-serine... 

Glyphosate or N-(phosphono-methyl) glycine Glycine derivative Inhibits amino acid synthesis nonselective, fast-acting herbicides Used as general weed control and weed control in transgenic maize 11-6... 

Imazapyr/ 2-[4,5-dihydro-4-methyl-4-(l-methyl ethyl)-5-oxo-lH-imidazol-2-yl]-3-pyridi necarboxylic acid Imidazolinones Amino acid synthesis inhibitor, nonselective Noncrop areas, railroad tracks, plantations 11-8... 

Efforts to develop a y amino acid synthesis in which the oxidation state need not be adjusted after coupling led to the hypothesis that y hydrazonoesters may be com petent radical acceptors. Would the stereocontrol model be applicable in the presence of an additional Lewis basic ester function in the hydrazone. This question was addressed via prototypical Mn mediated photolytic conditions with InCla as the Lewis acid. Successful coupling was achieved between isopropyl iodide and a variety of y hydrazonoesters 52a S2d (Table 2.7, entries 1 4) bearing methyl, dimethyl, and benzyloxy substituents at the position (1 to the hydrazone (a to the ester). Consistently high diastereoselectivities and excellent yields (91 98%) of the isopropyl adducts S3a S3d indicated that the substitution patterns examined in this study had little effect on reaction selectivity and efficiency. 

This group was developed as a water soluble carbamate in peptide synthesis. It is prepared hy methylating (2-phenylthio)ethylcarbamates of amino acids with methyl iodide and AgBp4. Amines may also be protected using Pms-4-nitrophenyl carbonate as a stable crystalline reagent that can be stored. The Pms group was cleavable with NaHCOi, hut Na2C03 was proved to be more efficient. ... 

The aromatic amino acid L-methyl DOPA (Di Hydroxy PhenylAlanine) 80 is used to make an antihypertensive compound. Synthesis by the Strecker method clearly requires the aromatic ketone 77, and the synthesis follows the pattern below.18 The intermediates and final product have been resolved in various ways. 

Another recent asymmetric amino acid synthesis involves the reaction of a methyl 2-isocyanoalkanoate (5) with I in the presence of -butyllithium or potassium t-butoxide to form the metalated imidazolinones 6 in situ. Alkylation of 6 results in chiral 4,4-disubstituted imidazolinones (7) often in optical yields of 90-1007o. The highest optical yields are obtained when R has a higher priority than R. In this case 7 has the (R)-configuration. Reversal of the priority results in the (S)-configuration. Hydrolysis of 7 to the chiral amino acid 8 requires rather drastic conditions and is best conducted with base. This method was reported for the synthesis of twenty 2-imidazoline-5-ones of type 7. ... 

Asymmetric amino acid synthesis. The reaction of aralkyl methyl ketones (2) with I as the chiral reagent in the presence of sodium cyanide in acetic acid affords... 

In the course of extending their studies of the generation of azomethine ylides from a-amino-acid esters Grigg et al. have discovered a simple one-step synthesis of N-substituted isoindolln-1-ones (Scheme 23). Treatment of -phthaldialdehyde (272) with a-amino-acids, their methyl esters, or a range of aryl or heterocyclic amines leads to isoindolin-1-ones (273) in moderate to good yields, probably via the mechanism shown. The reaction also works with aliphatic amines although less efficiently (26-40%). 

Folate mediates the transfer of one-carbon units into dilferent interrelated biochemical reactions. It is required for the synthesis of sulfur containing amino acids, epigenetic methylation and DNA synthesis. 

As applied to an amino acid synthesis, the ester enolate must react with another molecule that contains a nitrogen moiety. In one example, methyl 2-methylpropan-oate was treated with lithium diisopropylamide and then with 4-bromobutanenitrile to give 4.68. Catalytic hydrogenation of the cyano group gave methyl 6-amino-2,2-dimethylhexanoate (4.dP).35a in this case, the nitrile was the amine surrogate and the ester was the acid precursor. 

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