Protection of functional moieties

In designing the synthesis of a target-drug-molecule it is quite natural and also common that invariably more than one functional moiety is caused to participate in arriving at the various intermediates during the course of a synthesis. It is usually a common practice adopted by the research chemists to allow one particular moiety to function as the reactive 

Interestingly, a host of organic reactions are usually involved, having different specific experimental parameters, that do not eventually ensure reaction selectivity and under such critical situation(s) certain functional moieties need to be protected by first converting them into unreactive-structural-analogues . Hence, the protection of functional moieties may be accomplished by the help of a plethora of known organic reactions. 

All the reactions pertaining to protection of functional moieties may be summarized as stated below  

SOCI2 = Thionyl chloride CHgOH2 = Methanol onium ion HgO+ = Hydronium ion Pd = Palladium  

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The synthetic protocol for per-functionalized pillar[5]arene derivatives from per-hydroxylated pillar[5]arene can be applied to the synthesis of larger per-functionalized pillar[ ]arene derivatives. A per-hydro3tylated pillar[6]ar-ene with 12 phenolic moieties (3.7) was synthesized by Huang and Hou et al. (Scheme 3.3). 3.7 can be synthesized by de-protection of ethoty moieties (3.2) with BBts, which is the same method as used for the synthesis of per-hydrotylated pillar[5]arene. 

In fine wool such as that obtained from merino sheep, the cuticle is normally one cell thick (20 x 30 x 0.5 mm, approximate dimensions) and usually constitutes about 10% by weight of the total fiber. Sections of cuticle cells show an internal series of laminations (Figs. 1 and 2) comprising outer sulfur-rich bands known as the exocuticle and inner regions of lower sulfur content called the endocuticle (13). On the exposed surface of cuticle cells, a membrane-like proteinaceous band (epicuticle) and a unique hpid component form a hydrophobic resistant barrier (14). These hpid and protein components are the functional moieties of the fiber surface and are important in fiber protection and textile processing (15). 

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

Allylation and subsequent protection of the thus formed hydroxyl group furnishes compound 134, which bears the C-ring skeleton of baccatin HI. Removal of the C-9 silyl group, PhLi treatment of the resulting hydroxyl ketone, and in situ acetylation provides compound 135, which has the C-2 benzoate functionality. In the presence of a guanidinium base, equilibrium between the C-9 to C-10 carbonyl-acetate functional groups can be established. Thus, the desired C-9-carbonyl-C-10-acetate moiety 136 can be separated from the mixture. Compound 136 is then converted to aldehyde 137 via ozonolysis for further construction of the C-ring system (Scheme 7-40). 

FIGURE 3.1 Functional groups and the nature of the moieties used for their protection. Protectors incorporate the alkyl of an alcohol. 

High-resolution 13C NMR studies have been conducted on intact cuticles from limes, suberized cell walls from potatoes, and insoluble residues that remain after chemical depolymerization treatments of these materials. Identification and quantitation of the major functional moieties in cutin and suberin have been accomplished with cross-polarization magic-angle spinning as well as direct polarization methods. Evidence for polyester crosslinks and details of the interactions among polyester, wax, and cell-wall components have come from a variety of spin-relaxation measurements. Structural models for these protective plant biopolymers have been evaluated in light of the NMR results. 

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