Carboxyl groups, protection functional group

The next major obstacle is the successful deprotection of the fully protected palytoxin carboxylic acid. With 42 protected functional groups and eight different protecting devices, this task is by no means trivial. After much experimentation, the following sequence and conditions proved successful in liberating palytoxin carboxylic acid 32 from its progenitor 31 (see Scheme 10) (a) treatment with excess 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in ie/t-butanol/methylene chloride/phosphate buffer pH 7.0 (1 8 1) under sonication conditions, followed by peracetylation (for convenience of isolation) (b) exposure to perchloric acid in aqueous tetrahydrofuran for eight days (c) reaction with dilute lithium hydroxide in H20-MeOH-THF (1 2 8) (d) treatment with tetra-n-butylammonium fluoride (TBAF) in tetrahydrofuran first, and then in THF-DMF and (e) exposure to dilute acetic acid in water (1 350) at 22 °C. The overall yield for the deprotection sequence (31 —>32) is ca. 35 %. 

D-Glucofuranose with protected functional groups (99), when heated with hydrazine, gives a mixture of the hydrazinopyranose 100 and the pyridazine 101, which is transformed upon hydrolysis and oxidation into pyridazine-3-carboxylic acid. The mechanism was studied with labeled starting material. ... 

Carboxyl group protection. The a -esters of aspartic and glutamic acids are formed readily using the DCC method, after the geminal functionalities are sequestered (by reaction with EtiB). The acid can be regenerated under conditions lO.l M BU4NF) that do not affect an N-Boc group. 

One of the first works applying this approach was Kimura s synthesis of carboxylic acid-functionalized PHAs (mainly PGA) using the functional glycolide (benzyloxy-carbonyl)methyl-l,4-dioxane-2,5-dione [37]. Since then, this regime has been successfully extended to functionalized lactides offering a way of introducing (protected) functional groups such as protected amine, alcohol, and carboxylic acid [38]. In a similar fashion, Feijen has reported on the synthesis of morpholine-2,5-dione derivatives... 

The less hindered f/ans-olefins may be obtained by reduction with lithium or sodium metal in liquid ammonia or amine solvents (Birch reduction). This reagent, however, attacks most polar functional groups (except for carboxylic acids R.E.A. Dear, 1963 J. Fried, 1968), and their protection is necessary (see section 2.6). 

Thus the 42 functional groups in palytoxin carboxylic acid (39 hydroxyl groups, one diol, one amino group, and one carboxylic acid) were protected by eight different groups ... 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the... 

The efficiency of this method was demonstrated by the elegant two-step synthesis of aspartame [87], Protection of the a-amino group and activation of the a-carboxylic group are accomplished in only one step Deprotection of the amino functionality occurs during aminolysis, such as with methyl phenylalaninate (H-Phe-OMe in equation 15)... 

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