Amide group deprotection

This chemistry can be very powerful, since the amide product itself offers further possibilities for functionalisation by lithiation. The synthesis of the natural product ochratoxin A (section 9.1) illustrates this point. Two successive ortholithiations of carbamate 210 are used first to introduce one amide group and then a second, by anionic ortho-Fries rearrangement. The symmetrical diamide 211 can be allylated and then cyclised in acid, with concomitant hydrolysis of the second amide and deprotection of the phenol to yield a known intermediate... 

KHMDS in THF. The product 305 was isolated (45% yield, EfZ 75125) after deprotection of the /3-lactam amide group. 

The synthesis of the flexible Isoleucine-isobutyl compound (9, Scheme 2) was lengthier, mainly as a consequence of the fact that the compound contains a butyl-carboxamide group capable of picking up binding interactions on the ST side of the protein. Synthesis of the key isobutyl-sllyl-methylamine compound 10 was achieved over 8 steps. The amine was then coupled in standard fashion with the P2 portion of the molecule and the prime-side side chain was modified to the desired amide 11. Deprotection of the diphenyl-silane using TFA, as described above, provided the target diol 9. 

In peptide synthesis selective deprotection of C- or N-terminal groups is common in most methods of chain elongation. The amide groups offer some advantages for C-terminal protection (enhanced chemical stability and increased solubility in water). 

On the other hand, when intermediate 50 was subjected to the eonventional Heck reaction, it gave the 6-membered quaternary structure 51 in 87% yield rather than a 7-membered ring compound. Reduction of the amide group of 51 by LAH/AICI3 to amine was followed by deprotection of the ketal by acid to iso-13-demethoxyeiythratidinone (52) in 80% yield in two steps (Scheme 4). 

A copolymer of NiPAAm with 1 mol% of a vinyl monomer carrying a protected isocyanate group was used by Hiiata, Okazaki, and Iwata (2004) to fabricate cross-Unked coatings. Upon heat treatment at 150 °C for 1.5 h, the isocyanate group is deprotected and cross-links to the amide group of the NiPAAm unit. A dry layer thickness of 35 nm was obtained, but higher values are possible. Given that the substrate... 

This procedure is restricted mainly to aminodicarboxyhc acids or diaminocarboxyhc acids. In the case of neutral amino acids, the amino group or carboxyl group must be protected, eg, by A/-acylation, esterification, or amidation. This protection of the racemic amino acid and deprotection of the separated enantiomers add stages to the overall process. Furthermore, this procedure requires a stoichiometric quantity of the resolving agent, which is then difficult to recover efficiendy. Practical examples of resolution by this method have been pubUshed (50,51). 

Protective group chemistry for these amines has been separated from the simple amines because chemically they behave quite differently with respect to protective group cleavage. The increased acidity of these aromatic amines makes it easier to cleave the various amide, carbamate, and sulfonamide groups that are used to protect this class. A similar situation arises in the deprotection of nucleoside bases (e.g., the isobutanamide is cleaved with methanolic ammonia ), again, because of the increased acidity of the NH group. 

Two new sections on the protection for indoles, imidazoles, and pyrroles, and protection for the amide — NH are included. They are separated from the regular amines because their chemical properties are sufficienth different to affect the chemistry of protection and deprotection. The Reactivity Charts in Chapter 8 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first discussed. 

In this series of amides, hydrolysis or aminolysis of a simple ester, cleavage of a silyl groups a cis/trans isomerization, or reduction of a quinone to a hydro-quinone exposes an alcohol that then induces deprotection by intramolecular addition to the amide carbonyl. 

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