O-protection

Peptide synthesis requires the use of selective protecting groups. An N-protected amino acid with a free carboxyl group is coupled to an O-protected amino acid with a free amino group in the presence of dicydohexvlcarbodi-imide (DCC). Amide formation occurs, the protecting groups are removed, and the sequence is repeated. Amines are usually protected as their teit-butoxy-carbonyl (Boc) derivatives, and acids are protected as esters. This synthetic sequence is often carried out by the Merrifield solid-phase method, in which the peptide is esterified to an insoluble polymeric support. 

In contrast to the intermediate hydroxystannanes, O-protected stannanes 7 are stable compounds which can be distilled or chromatographed and stored under nitrogen for months. Treatment of 7 with butyllithium in tetrahydrofuran at — 78,JC results in rapid tin/lithium exchange (< 1 min). No products resulting from Wittig rearrangement or formation of an ate complex 8 could be detected9. 

The reactions of various 2-butenyltitanium and -zirconium reagents with 2-(benzyloxy)propanal (and other O-protected derivatives) also proceed with low induced diastereoselectivity90. 

TV-aluminum imines are another example of masked inline derivatives of ammonia. They are easily synthesized by partial reduction of nitriles with diisobutylaluminum hydride (D1BAL-H)6. Addition of lithium organic reagents to /V-aluminum iniines 7 derived from O-protected cyanohydrins 6 provides a-amino alcohols 8a and 8b in moderate yields and low to good diastereo-selectivities n 12. 

In the case of an oxygen substituent at C-3 varying selectivities are observed, depending on the O-protective group, the Lewis acid, and the nucleophile. 

I Stratospheric ozone, O, protects life on Farth from harmful ultraviolet radiation from the Sun. Suggest two Lewis structures that contribute to the resonance structure for the 02 molecule. Experimental data show that the two bond lengths are the same. 

The intramolecular /zetero-Diels-Alder reactions of 4-O-protected acyl-nitroso compounds 81, generated in situ from hydroxamic acids 80 by periodate oxidation, were investigated under various conditions in order to obtain the best endo/exo ratio of adducts 82 and 83 [65h] (Table 4.15). The endo adducts are key intermediates for the synthesis of optically active swainsonine [66a] and pumiliotoxin [66b]. The use of CDs in aqueous medium improves the reaction yield and selectivity with respect to organic solvents. 

N-Acylnitroso compounds 4 are generated in situ by periodate oxidation of hydroxamic acids 3 and react with 1,3-dienes (e.g. butadiene) to give 1,2-oxazines 5 (Scheme 6.3). The periodate oxidation of 4-O-protected homo-chiral hydroxamic acid 6 occurs in water in heterogeneous phase at 0°C, and the N-acylnitroso compound 7 that is generated immediately cyclizes to cis and tranx-l,2-oxazinolactams (Scheme 6.4) [17a, b]. When the cycloaddition is carried out in CHCI3 solution, the reaction is poorly diastereo-selective. In water, a considerable enhancement in favor of the trans adduct is observed. 

The O-protected lactam 197a is aminated by ammonia and HMDS 2 on heating to 130°C in a pressure bottle with catalytic amounts of Ts0H-H20, via 198a and... 

For further discussion of synthetic applications of the carbanions of O-protected cyanohydrins, see J. D. Albright, Tetrahedron, 39, 3207 (1983). 

The stereochemistry was controlled by Lewis acid-induced addition of these allylic silanes to aldehydes. The reaction of the silane with O-protected (S)-3-hydroxy-2-methylpropanal provides 15. The silane reacted with the benzyl-protected analog to provide 16. 

Lehmann, G., Neunhoeffer, O., Roselius, W., Vitzthum, O., Protection of autoxidizable materials by addition of extract of green coffee beans, US 3,663,581, 1972. (CA77 60335n)... 

SCHEME 7. Montmorillonite K-10 catalyzed glycosidation of a 3,4-di-O-protected olivose with various alcohols. 

With a view to increasing the selectivity in OZT formation (i.e. reducing the number of products shown in Scheme 23), selective hydroxyl protections were performed. Protection of the C-l alcohol would induce limitation to fused structures (Scheme 25),10 whereas 3-O-protection would only allow formation of s/hro-derivatives (Scheme 26).47... 

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