Carbamates, hydrolysis

Carbamate hydrolysis is frequendy observed as the initial reaction for pesticides having carbamate bonds, such as aldicarb, carbofuran, carbaryl, and benomyl (eq. 12) (19). Numerous genera of carbamate-hydroly2ing bacteria have been identified, including Pseudomonas, Jhihrobacter, Bacillus, Nocardia, Achromobacter, Flavobacterium, Streptomyces, Alcaligenes, A spirillum, Micrococcus, and Bhodococcus. 

H-1,3-Benzoxazine-2,4(3H)-dione (7.98) is an interesting cyclic carbamate. Hydrolysis of the ester group likely yields the ring-opened carbamic acid 7.99 as an undetected intermediate, which very rapidly decarboxylates to form the product salicylamide (7.100). When the cyclic carbamate was ad-... 

The sulfamate saxitoxins have very low potencies relative to their carbamate hydrolysis products. This relationship has been observed in every assay system tried, including the standard mouse bioassay (Figure 3), squid giant axon (1 ), frog sciatic nerve (16), mammalian brain (1 ), and single rat sarcolemma sodium channels incorporated into lipid bilayers (15). It seems unlikely that human oral potencies are an exception to this trend. 

The pesticides methyl and ethyl parathion were determined in run-off water er preconcentration on XAD-2. This allowed analyses of these compounds at the parts per billion level (497). Parathion and paraoxon obtained from leaf extracts and orchard soil have also been determined (492). The separation of 30 carbamate pesticides by RPC has been described (493). Various modes of postcolumn fluorometric detection of carbamate insecticides have been reported including post-colun)n reaction between o-phthalaldehyde and methylamine, a carbamate hydrolysis... 

The enantiomerically pure oxazolidinone derivative 7 (Scheme 4),14,20 was converted into the metathesis precursor 6 by a sequence of carbamate hydrolysis, amide alkylation and protection of the secondary alcohol as the TBDMS ether in a 95% overall yield. Subsequent [Ru-1] catalysed ROM-RCM converted 6 into the desired dihydropyrrole 5. 

When taken with meals, a 30% increase in absorption of the drug was observed, with peak plasma concentrations occurring within 2.5-4 h after oral administration. When coadministered with ritonavir, the overall half-life is improved to 15 h.20 Darunavir (1) has been shown to be metabolized by liver enzyme CYP450 (3A4).21 22 Thus when administered with low-dose ritonavir—a CYP450 and protease inhibitor—bioavailability increases from 37% to 84%. Absorption of darunavir occurs primarily in the intestine through passive intracellular diffusion. Darunavir and its metabolites are excreted primarily in the feces and urine.23 Metabolism occurs via, carbamate hydrolysis, aliphatic hydroxylation, aromatic hydroxylation, and other metabolites. 

Hegarty AG, Frost LN. Isocyanate intermediate in ElCb mechanism of carbamate hydrolysis./. Chem. Soc. Chem. Commun., 1972, pp. 500-501. 

Carbamate hydrolysis syn Elimination Dipolar cycloaddition [2,3]-Sigmatropic rearrangement... 

Scheme 3 Carbamate hydrolysis in alkali. Subscript Lg refers to substituent change in the leaving group (-OAr) subscript Nuc refers to substituent change in the nucleophile. / sc refers to change in effective charge...

Amides from Esters Hydrolysis of Ureides Hydrolysis of Carbamates Hydrolysis of Carboxamides Decarboxylation ... 

Metabolism of mebendazole occurs primarily by reduction of the 5-carbonyl to a secondary alcohol, which greatly increases the water solubility of this compound. An additional Phase I metabolite resulting from carbamate hydrolysis has been reported as well. Both the secondary alcohol and the amine are readily conjugated (a Phase II metabolism). Evidence would suggest that the anthelmintic activity of mebendazole resides in the parent drug and none of the metabolites. 

Analogues 249 (X = H, OH) of UDP-GlcNAc have been prepared as potential inhibitors of chitin synthetases. The synthetic route involved a C-allyl derivative of GlcNAc, which was elaborated by ozonolysis, Wittig reaction and coupling with the nucleoside, followed by hydrogenation or hydroxylation as appropriate. The corresponding amides were also prepared from 5 -amino-5 -deoxyuridine. Lipophilic amino acid methyl esters and methylamides have been coupled to 0-5 of AZT by carbamate links. The products showed anti-HIV activity, but this was not due to carbamate hydrolysis or to direct inhibition of reverse transcriptase, and the mechanism of action may be one not previously observed with nucleoside antivirals. ... 

Similarly, diphenyl phosphate as amidinium salt 18 acts as a stable transition-state analogue for carbonate 19 and carbamate hydrolysis [27] (for a detailed review, see [1]). 

The reactivity of 6-quinolinyl (28) and 8-quinolinyl At,At-dimethylcarbamate (29) was examined in several aqueous basic media. A quadratic dependence upon hydroxide concentration was observed for both compounds, which is typical of a mechanism (Scheme 12) involving a base-catalysed deprotonation of the tetrahedral intermediate (Ti ) with the formation of a dianion (T2 ) at high concentrations of hydroxide ion, while at lower concentrations, a specific-base catalysed addition-elimination mechanism seemed to be predominant. The reactivity of 8-quinolinyl lV,lV-dimethylcarbamate (29) was also studied in several amine buffers, showing specific base catalysis. The reactivity of 6-quinolinyl At,A-dimethylcarbamate (28) was studied in H2O and D2O and the solvent isotope effect supports a mechanism involving a specific base hydrolysis. All results confirmed the existence of a mechanism with a rate-determining step involving the substrate anion and a second mole of hydroxide ion. This mechanism was hitherto unknown for carbamate hydrolysis, being known to occur only with amides. ... 

Shi Z, Griffin JA. Catalysis of carbamate hydrolysis by vancomycin and semisynthetic derivatives. J Am Chem Soc 1993 115 6482-6486. 

An overall reaction in the case of carbamate hydrolysis for CO2 absorption may be written, using (5.2.13), as follows ... 

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