Protective groups acids

JP Tam, MW Rieman, RB Merrifield. Mechanisms of aspartimide formation the effects of protecting groups, acid, base, temperature and time. Pept Res 1, 6, 1988. 

The second platform of ester-protected positive resists designed for ArF lithography is the alicyclic polymer platform,which was first developed at the University of Texas at Austin,and involves resists in which the alicyclic units with pendant ester-protecting groups, acidic groups, and adhesion-promoting groups constitute the backbone of the polymer. Resist polymers of this platform... 

The hydroxyketone, protected with isopropenyl methyl ether, (73) is coupled to the protected C6-lithium acetylenide 80. The Cj -triol 87 is formed after removal of the protecting groups. Acid-catalysed dehydration of 87 leads to the Ci5-diol 88, which is partially produced in the (9Z)-form. The (9 )-compound must be isolated by crystallization from the ( 7Z)-mixture of the acetylenic Cis-phosphonium chloride 89 prepared in the conventional manner. Successive partial hydrogenation of (E)-89, palladium-catalysed isomerization, and crystallization, give 86 in an overall yield of 43% based on 73. 

PROTECTING GROUPS stable to base and mild acid... 

Protection and activation give us a reagent for the synthon CH2CO2H. AVe protect the acid as an ester and add another ester group as activation, giving malonic ester CH2(C02Et)2. How would you make TM 57 ... 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Trichloro- and 2,2,2-tribromoethoxycarbonyl (Tceoc and Tbeoc) protecting groups are introduced with the commercially available 2,2,2-trihaloethyl chloroformates. These derivatives are stable towards CrOj and acids, but can smoothly be cleaved by reduction with zinc in acetic acid at 20 °C to yield 1,1-dihaloethene and CO. Several examples in lipid (F.R. Pfeiffer, 1968, 1970) and nucleotide syntheses (A.F. Cook, 1968) have been described. 

The only acid-resistant protective group for carbonyl functions is the dicyanomethy-lene group formed by Knoevenagel condensation with malononitrile. Friedel-Crafts acylation conditions, treatment with hot mineral acids, and chlorination with sulfuryl chloride do not affect this group. They have, however, to be cleaved by rather drastic treatment with concentrated alkaline solutions (J.B. Basttis, 1963 H. Fischer, 1932 R.B. Woodward, 1960, 1961). 

In step 1 of each oligonucleotide-synthesis cycle the 5 -terminal 4,4 -dimethoxytrityl protecting group is removed with trichloroacetic acid, and the support is washed with acetonitrile to prevent dctritylation of the next incoming phosphoramidite. The 4,4 -dimethoxy-... 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain pro-teaing groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N -deprotection. Only /ert-butyl esters and carbamates ( = Boc) are solvolyzed in this mixture. 

APA may be either obtained directly from special Penicillium strains or by hydrolysis of penicillin Q with the aid of amidase enzymes. A major problem in the synthesis of different amides from 6-APA is the acid- and base-sensitivity of its -lactam ring which is usually very unstable outside of the pH range from 3 to 6. One synthesis of ampidllin applies the condensation of 6-APA with a mixed anhydride of N-protected phenylglydne. Catalytic hydrogenation removes the N-protecting group. Yields are low (2 30%) (without scheme). 

It is widely recognized that an allyl group is a useful protecting group for acids, amines, and alcohols. Facile formation of a Tr-allylpalladium complex from... 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Another protecting group of amines is 1-isopropylallyloxycarbonyl, which can be deprotected by decarboxylation and a /3-elimination reaction of the (tt-l-isopropylallyl)palladium intermediate under neutral conditions, generating CO2 and 4-methyl-1,3-pentadiene. The method can be applied to the amino acid 674 and peptides without racemization[437]. 

C6H5CH2OC—) IS one of the most often used ammo protecting groups It is attached by acylation of an ammo acid with benzyloxycarbonyl chloride... 

Just as It IS customary to identify individual ammo acids by abbreviations so too with protected ammo acids The approved abbreviation for a benzyloxycarbonyl group IS the letter Z Thus N benzyloxycarbonylphenylalanine is represented as... 

Alternatively the benzyloxycarbonyl protecting group may be removed by treat ment with hydrogen bromide m acetic acid... 

---