Deprotection, selective methods

Selective methods for deprotecting glycopeptides either at the amino or at the carboxyl terminus have been developed during the past decade by introduction and application of different combinations of protecting groups (Table II). 

Dialkyl 1-aminoalkylphosphonates are excellent substrates for the synthesis of peptides with a C-terminal phosphonate moiety. The DCC (Scheme 10) and active ester methods (Scheme 11) provide good to excellent yields of the product protected at the N-terminal and P-terminal. Several selective methods to remove the protecting groups are available. Total deprotection is achieved by the action of HBr in AcOH. 

Maiti and Roy reported a selective method for deprotection of primary allylic, benzylic, homoallylic and aryl TBS ethers using aqueous DMSO at 90° C. All other TBS-protected groups, benzyl ethers, THP ethers as well as methyl ethers remain unaffected. 

The parent spacer, 4-hydroxybutanoic acid, spontaneously undergoes loss of water under acidic or basic conditions to give 4-butyrolactone. To prevent cyclization when the spacer is coupled to methoprene, both the hydroxyl and carboxyl functions had to be protected and selectively deprotected. The methods used are summarized in Figure 2. The protection/deprotection chemistry described was originally developed for use in the field of peptide synthesis. 

O 12. Bunce, R.A. Hertzler, D.V. A Selective Method for Oxygen Deprotection in Bistrimethylsilylated Terminal Alkynols J. Org. Chem. 1986,573451-3453... 

Once the acetates have served their purpose their removal is most easily effected by the Zemplen procedure [54] (catalytic NaOMe in MeOH) (Methods 16 and 17) but more selective methods—such as guanidine in ethanol [55], or DBU in benzene (Figure 2.38) [56]—can leave less reactive benzoate esters intact. For deprotection, lipases can again offer exquisite discrimination between acetates which can be particularly useful in sensitive substrates where classical methods fail. An idea of the selectivity that can be attained is given in Figure 2.39 which shows the specific sites of deacetylation in peracetyl sucrose using lipases from different organisms [57]. 

The 1,3-oxathiane 8, derived from (5)-l,2,4-butanetriol, is lithiated to form the equatorial anion 9, which adds benzaldehyde with high induced but moderate simple diastereoselectivity (4 1) to form the alcohols 10 and 1117. The selectivity is enhanced to 7 1 by metal exchange by means of magnesium bromide. Deprotection affords (5)-2-hydroxy-l,2-diphenylethanone with 75% ee. It is expected that the method could be extended to aliphatic aldehydes. 

As they are available from natural sources in enantiomerically pure form, carbohydrates are useful starting materials for syntheses of enantiomerically pure compounds. However, the multiple hydroxy groups require versatile methods for selective protection, reaction, and deprotection. Show how appropriate manipulation of protecting groups and/or selective reagents could be used to effect the following transformations. 

G. D. Kishore Kumar and S. Baskaran, A facile, catalytic, and environmentally benign method for selective deprotection of ferf-butyldimethylsilyl ether mediated by phosphomolybdic acid supported on silica gel, /. Org. Chem., 70 (2005) 4520-4523. 

A brief exposure of diacetate derivatives of aromatic aldehydes to MW irradiation on neutral alumina surface rapidly regenerates aldehydes (Scheme 6.5) [36], The selectivity in these deprotection reactions is achievable by merely adjusting the time of irradiation. As an example, for molecules bearing acetoxy functionality (R = OAc), the aldehyde diacetate is selectively removed in 30 s, whereas an extended period of 2 min is required to cleave both the diacetate and ester groups. The yields obtained are better than those possible by conventional heating methods and the procedure is applicable to compounds bearing olefmic moieties such as cinnamaldehyde diacetate [36],... 

Methods of Selective Deprotection, Followed by Peptide-Chain Elongation... 

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