Functionalization of the side-chain

The preparation of 3-vinylpyrroles was investigated utilizing the Horner-Wads worth-Emmons reaction with 3-formyl-lV-tosylpyrrole 06S1494 . The intramolecular acylation of pyrrole-2-Weinreb amides provided access to novel indolizinone derivatives 06T6182 . The amidation of pyrrole-2-carbonyl chloride was utilized as a key step in the preparation of pyrrole-oxazole analogue 90 of the insecticide Pirate 06S1975 . 

A Mitsunobu reaction of 3,4-dihydroxypyrroles was utilized to prepare 3,4-dialkylenedioxypyrroles (i.e., 91) 06TL3521 . 

The large scale preparation of orthogonally protected pyrrole tricarboxylic acid derivatives (i.e., 92) was reported. A key step was the selective a-chlorination of a 2,4-dimethylpyrrole intermediate that was derived from the Knorr pyrrole synthesis. 

An asymmetric Michael addition reaction to a,(i-unsaturatcd /V-acylpyrrolcs was developed 07TL2815 . The reaction was mediated by a La-based BINOL catalyst system. 

Another unexpected side reaction occurred in the attempted deprotection of pyrrole acetal 70 07OL4785 . Treatment of 70 with iodine (mild Lewis acid) led to the formation of the novel pyrrole macrocycle, cyclononatripyrrole 71. 

Gold-mediated asymmmetric Michael addition reactions onto a,p-unsaturated N-acylpyrroles were investigated 05JA514 . 

Selective Birch reductions were investigated with a number of electron-rich fused pyrrole substrates 05JOC2054 . Deprotonation of phenol 79 followed by treatment of phenoxide 80 with sodium metal in ammonia gave 81. The same reaction with the corresponding 7-methoxy derivative gave a mixture that contained over-reduced products. 

Pyrrolo[l,2-l)]isoquinolines have been prepared by an intramolecular cyclization onto pyrrole Weinreb amides or morpholine amides 05T3311 . 

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In analogy, Ugi et al. reported on a lactam formation by running a one-pot three components reaction the condensation of L-lysine 7, isobutyraldehyde and methyl isocyanide led to the corresponding a-amino-c-caprolactam 9, but the yield was not given. The authors presumed either a nucleophilic substitution of the ester 8 as the primary Ugi product by the amino function of the side chain or, alternatively, the nucleophilic attack of the NH2-group on an intermediately formed 0-acylamide and a subsequent rearrangement (Scheme 1) [4]. 

The reaction occurs with the 17,21-dihydroxy-20-keto functionalities of the side chain, and is also specific for these corticosteroids [104]. 

Wall et al. built a binuclear copper(II) complex 43 in order to see acceleration of phosphodiester cleavage (52). With the substrate (50 p.M) shown, the reaction might be considered as a model for the first step of the hydrolysis of RNA, in which the alcohol function of the side chain intramolecularly attacks the Cun-activated phosphate as a nucleophile for a ring closure reaction. Compared to an analogous mononuclear complex 44 (at 1 mM), a rate constant ca. 50 times larger for 43 (at 1 mM) was observed at 25°C and pH 7, implying that the two metal ions probably cooperate. An analogous zinc(II) complex 45 was reported only as a structural model for the active site of phospholi-... 

Furthermore, due to its structural similarity to histamine (R)-a-methylhistamine (12) shows high affinity for histamine methyltransferase (HMT). Accordingly, methylation of the imidazole ring by HMT accounts for the short plasma half-life of (/ )-a-methylhistamine (12) in man (tVl = 3 min) [6], It is assumed that the primary amine functionality of the side chain plays a key role in the interaction between... 

A few derivatives of taxol and of deacetylbaccatin III have been synthesized in which the dilferent hydroxyl groups have been modified for structure-activity studies these are described later in Section VII, which deals with pharmacology. However, three reactions bear special mention (a) the intramolecular cyclization of the side chain of taxol leading to the oxazolone (24) (43), (b) an approach to the functionalization of the side chain via vicinal dihydroxylation (11,46) of the cinnamate (25) to give 26, and (c) Sharpless oxyamination leading to mixtures of 2 - and 3 -oxyaminated products (see below). 

E.J. Corey and co-workers synthesized the cdc25A protein phosphatase inhibitor dysidiolide enantioselectively. In the last phase of the total synthesis, the secondary alcohol functionality of the side-chain was established with a highly diastereoselective oxazaborolidine-catalyzed reduction using borane-dimethylsulfide complex in the presence of the (S)-6-methyl CBS catalyst. Finally, a photochemical oxidation generated the y-hydroxybutenolide functionality. This total synthesis confirmed the absolute stereochemistry of dysidiolide. 

Figure 18. (Left) SFM images of poly(r -butylacrylate) brushes with varying degree of polymerization, n, of the polyfn-butylacrylate) side chains on mica (spin cast samples). (Right) Persistence length of a molecular brush as a function of the side chain length n. The continuous line describes the power function lp

NH ib is a significant component of a number of modes in the 1400- to 1200-cm region, mixing differently in different parts of this region and as a function of the side-chain structure. As has been noted (Hsu et al., 1976), it is therefore not possible to expect a simple general relationship between such a frequency and the backbone conformation (Lord,... 

The synthesis of cephalotaxine esters has been motivated by the recognition of the antitumor properties associated with some of these compounds, most notably homoharringtonine. Most, if not all, of their syntheses focus on the efficient preparation of the side chains and methods of esterification of the intact cephalotaxine nucleus, usually obtained from natural sources, where it is far more abundant than any of the corresponding esters. Because of the hindered nature of the cephalotaxyl alcohol, many approaches rely on partial esterification and further functionalization of the side chains. 

The 2,3,6-trisubstituted piperidine alkaloids are widely distributed in nature and have a common structure possessing 3-hydroxypiperidine ring with a side chain in position 6 and methyl or hydroxymethyl group in position 2. They are distinguished by the configuration of the substituents, the length and functionality of the side chain in position 6. 

Damascones. The damascones are isomers of the corresponding ionones in which the a,p-unsaturated function of the side chain has been transposed. They occur in rose oils and their name is derived from the Damask rose (Rosa damascena) in which they were first detected. They have powerful fruity odours with a hint of florality and rose character. 

Schubert and coworkers explored the use of pentafluoroslyrene and its copolymerization with styrene to obtain homo- and copolymer scaffolds for further functionalization with protected thiosugars via a thiol-para-fluoro click reaction (Figure 2.14). The first functionalization of the side chains resulted in about 60% conversion. Subsequent functionalization led to an increase in side chain conversion of up to 90%. The observed increase in functionalization could also be applied in a stepwise fashion to give access to heteromultivalent glycocopolymers. Selected copolymers showed self-assembly into spherical nanoparticles during nanoprecipitation with diameters ranging from 70 to 720 nm. 

Pteridine formation occurs chemoselectively the primary condensation step is likely to proceed via the nitroso group giving rise to the imine 5, which cyclizes via the remaining NH2 group with the terminal function of the side chain (C=0, ester, nitrile, etc.). 

The amino function of the side chain of ornithine has been protected as described or directly in aqueous medium without protecting the carboxylic acid function (eq 13). The protected ornithine has been used in the synthesis of Ramoplanin,... 

Reaction with N-Bromosuccinimide (MBS). The behaviour of 2-sul-fenylated-tryptophan peptides towards NBS is of particular interest, since NBS can be used to modify this amino acid residue in proteins (see Section III.2.1.). In the following scheme, the reactions occurring upon treatment of a 2-sulfenylated tryptophan peptide with NBS are shown. Bromination at the 3-position of the indole moiety is followed by displacement of the halogen atom by the carbonyl function of the side chain amide, with concomitant cyclization to an imido-lactone (165). 

In nucleotides however, position 5 is not free for acetal formation and the additional hydroxyl functions of the side chain can not form a macrocyclic ring for steric reasons (24). The anomalous thiohemiacetal stability towards hydrolysis cannot be simulated at the lumiflavin or riboflavin level, while experiments with 8a-oxo-FMN or -FAD are lacking. 

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