Protective groups methyl ester

In a recent modification of the second synthesis (50S) effected for fluvibactin (45) an o-xylene protection group was proposed (reaction of 2,3-dihydroxy-benzoic acid methyl ester with 1,2-di(bromomethyl)benzene) which could be removed later by hydrogenolysis. The formation of the oxazoline ring from protected DHB-L-threonine methyl ester was achieved with Mo(VI) catalysts (e.g. (NH4)2Mo04) without affecting the chiral centers. Derivatization of the primary amino groups of norspermidine with the protected DHB methyl ester was catalyzed by Sb(OC2115)3. 

Very recently, Mordini and coworkers" have overcome the problems associated with the long reaction times that are normally required for the synthesis of hydroxamic acids from esters by performing these transformations under MW irradiation. The protective groups are also well tolerated under these reaction conditions, though a partial deprotection of the feri-butoxycarbonyl (Boc) group was observed in the reaction with Boc-proline ester. Amidic bonds and ketals also survive without any detectable decomposition. All the reactions go to completion in about six minutes, except in the case of the conversion of Boc-protected phenylalanine methyl ester, which required longer reaction times (12 min). 

In the case of the double NPS-protected lysine methyl ester, oxidation selectively takes place at the 6-sulfenamide function under spontaneous cyclization via the a-sulphe-namido group as nucleophile. Only one diastereoisomer of the A,A -bis(NPS)-protected methyl 6-amino-piperidine-2-yl-carboxylate seems to be formed. The transformation of a-amino alkanoates and diaryl or dialkyl disulfides to the aryl- or alkylsulfenimine derivatives can be performed electrochemically using MgBr2 as a mediator system. This reaction can either proceed in one step or starting from the corresponding sulfenamide [170]. 

Nucleophilic tert-prenylation. When using prenylboranes instead of tert-prenylboranes, tert-prenylation of 3-chloroindolenines becomes possible. The Danishefsky tert-prenylation has also been extensively used for the synthesis of 3-tert-prenylindoles which can be obtained from 2-tert-prenylated precursors (see Sect. 4). The 1995 synthesis of the acyl-CoA-cholesterol acyltransferase inhibitor gypsetin (94) [91, 92] was the first occasion to publish that elegant reaction (Scheme 19) [88, 93]. On treatment of phthalimide-protected tryptophan methyl ester (85) with tcrt-BuOCl, the 3-chloroindolenine is formed in sim, which is nucleophilicaUy attacked by prenyl-9-BBN with regioinversion of the prenyl group. Hydrazinolysis afforded 2-tert-prenyltryptophan methyl ester (91). 

In order to activate or enhance the activity of group III of the metabotropic glutamate receptors, new and potent phosphinic agonists were synthesized by Acher et al. in 2007 [54], Indeed, these presynaptic receptors inhibit the adenylate cyclase and the release process. y-Phosphinic acid derivative 49 is the key intermediate for the formation of compounds 51,52 and 53 (Scheme 7). Starting from a radical addition of hypophosphorous acid to the IV-CBz protected vinylglycine methyl ester 48, the phosphinic derivative compound 49 was obtained in 94%... 

For protecting carboxyl groups, methyl esters (OMe), ethyl esters (OEt), benzyl esters (OBZL), p-nitrobenzyl esters (ONB), /-butyl esters (OBut) or substituted hydrazides (e.g., —N2H2—Z) are used. Coupling occurs according to the azide method. 

Reaction with Amino Alcohols and Related Compounds. Both secondary and tertiary carbamates bearing a vicinal hydroxyl group react with carboxylic acids in the presence of DEAD and TPP to afford the corresponding esters with inversion of configuration (eq 34). Reaction of N-t-butoxycarbonylserine with methanol, DEAD, and TPP gives the corresponding methyl ester in >98% yield (eq 35). Without methanol, TV-benzyloxycarbonyl- or A-f-butoxycarbonylserine reacts with the preformed adduct of DEAD and TPP to afford the P-lactone (eq 35). The W-protected serine methyl ester (37a) and threonine methyl ester (37b) react with DEAD and TPP to give the dehydrated products (38a) and (38b) (eq 36). ... 

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

Section 27 16 Carboxyl groups are normally protected as benzyl methyl or ethyl esters Hydrolysis m dilute base is normally used to deprotect methyl and ethyl esters Benzyl protecting groups are removed by hydrogenolysis... 

Mocimycin has been chemically converted to aurodox by protection of the 4-hydroxy group at the pyridone moiety as the benzoylformate, followed by /V-methylation and hydrolytic removal of the protective group (1,55). Whereas aurodox esters are active growth promotors in animals, goldinamines that are A/-acylated by acids other than goldinonic acid, such as acetic, benzoic, or arylsulfonic acids, lack useful antimicrobial or growth-promoting activity (1). 

Me3SiI, CH3CN, 25-50°, 100% yield. Selective removal of protective groups is possible with this reagent since a carbamate, =NCOOCMe3, is cleaved in 6 min at 25° an aryl benzyl ether is cleaved in 100% yield, with no formation of 3-benzyltyrosine, in 1 h at 50°, at which time a methyl ester begins to be cleaved. 

The protective group is removed by mildly alkaline conditions that do not cleave methyl or benzyl esters. The group is stable to CF3COOH, HCl-AcOH, and HBr-AcOH. A polymer-bound version of this group has also been developed. ... 

Viprostol (81) also incorporates a hydroxy group moved to C-16 and protects this from facile metabolic oxidation by vinylation. It is a potent hypotensive and vasodilatory agent both orally and transdermally. The methyl ester moiety is rapidly hydrolyzed in skin and in the liver so it is essentially a prodrug. It is synthesized from protected E-iodo olefin 78 (compare with 75) by conversion to the mixed organocuprate and this added in a 1,4-sense to olefin 79 to produce protected intermediate 80. The synthesis of viprostol concludes by deblocking with acetic acid and then reesterification with diazomethane to give 81 [19]. 

The amino group of alanine is protected as the Boc derivative, and the carboxyl group of leucine is protected as the methyl ester. 

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