Biologically important compounds alcohols

Having succeeded in obtaining the first results from a catalytic asymmetric nitroaldol reaction, we attempted to apply the method to the catalytic asymmetric synthesis of biologically important compounds. The nitroaldol products were readily converted into /3-amino alcohols and/or ct-hydroxy carbonyl compounds and convenient syntheses of three kinds of optically active /1-blocker are presented in Sch. 8 [55-57]. 

The Sharpless asymmetric aminohydroxylation [552] of the electron-deficient 2-vinylfuran 469 gives a 7 1 mixture of semi-protected amino-alcohols 470 and 471 (41%). The major product 472 (ee > 86%) was reduced by diisobutylaluminum hydride giving a diol [553] which is then converted into the /3-hydroxyfurylamine derivative 473, an important synthetic building block for various biologically important compounds, including l,5-dideoxy-l,5-imino-alditols such as 474 (O Scheme 110). A less regioselective, but shorter way to intermediate 473 is the direct asymmetric aminohydroxylation of vinylfuran [554,555]. 

The Cr(salen)-catalyzed ARO could be applied to prepare a range of chiral building blocks useful for the synthesis of biologically important compounds. Practical routes to cyclic cis- and trans-l,2-amino alcohols have been developed using Cr(salen) catalysis [11]. ARO methodology also enabled the enantioselec-tive synthesis of the core structures of balanol [12], prostaglandin derivatives... 

Many biologically important compounds are alcohols. Because of their charaeteristic pleasant odor many alcohols, for the instance menthol and citronellol are used in the preparation of perfumes. An alcohol with a more eomplex molecular structure is cholesterol, which is a component of cellular membranes and the starting compound for the biosynthesis of various hormones. 

Amino alcohols, which have a broad spectrum of biological activities, can be categorized as adrenahne-like with one chiral center at C-1 or as ephedrine-like with two chiral centers at C-1 and C-2 (Scheme 7). Although a variety of methods have been developed for the stereoselective preparation of 1,2-amino alcohols, " in most cases it is easier and more efficient to prepare these important compounds stereoselectively starting from chiral cyanohydrins (Scheme... 

The enantioselective reduction of unsaturated alcohol derivatives has been applied to the synthesis of several biologically active compounds (Scheme 24.12). Warfarin (123, R=H) is an important anticoagulant that is normally prescribed as the racemate, despite the enantiomers having dissimilar pharmacological profiles. One of the earliest reported uses of DuPhos was in the development of a chiral switch for this bioactive molecule, facilitating the preparation of (R)- and (S)-warfarin [184]. Although attempted reduction of the parent hydroxycoumarin 122 (R=H) led to formation of an unreactive cyclic hemiketal, hydrogenation of the sodium salt proceeded smoothly with Rh-Et-DuPhos in 86-89% ee. 

The asymmetric reduction of prochiral ketones to their corresponding enantiomerically enriched alcohols is one of the most important molecular transformations in synthetic chemistry (20,21). The products are versatile intermediates for the synthesis of pharmaceuticals, biologically active compounds and fine chemicals (22,23). The racemic reversible reduction of carbonyls to carbinols with superstoichiometric amounts of aluminium alkoxides in alcohols was independently discovered by Meerwein, Ponndorf and Verley (MPV) in 1925 (21—26). Only in the early 1990s, first successful versions of catalytic... 

The preparation of stereochemically-enriched compounds by asymmetric acyl transfer using chiral nucleophihc catalysts has received significant attention in recent years [1-8]. One of the most synthetically useful and probably the most studied acyl transfer reaction to date is the kinetic resolution (KR) of ec-alcohols, a class of molecules which are important building blocks for the synthesis of a plethora of natural products, chiral ligands, auxiliaries, catalysts and biologically active compounds. This research area has been in the forefront of the contemporary organocatalysis renaissance [9, 10], and has resulted in a number of attractive and practical KR protocols. 

Many publications are devoted to the synthesis of nitrile complexes, carried out by the immediate (direct) interaction of RCN and MX , mostly in the absence of a solvent [10, p. 95]. A series of N-donors, N-containing heterocyclic donors, whose complexes frequently model biologically important objects (Sec. 2.2.42), should be mentioned apart. The following compounds belong to this type azoles 188, azines 189, and their amino derivatives 572. Their interaction with metal salts takes place usually without a solvent with the use of liquid heterocyclic ligands, for example pyridine [10, ch. 4, p. 107 11], in alcohol or alcohol-aqueous mediums in cases of crystalline ligands (3.10)—(3.12). The specific conditions are presented in the literature, cited in Sec. 2.2.4.2. 

The hydrocyanation reactions of electrophilic aldehydes, ketones and their corresponding imines gives direct access to synthetic derivatives of several important structures, including a-hydroxy carboxylic acids, / -amino alcohols and a-tertiary and a-quaternary-a-amino acids. The asymmetric hydrocyanation reaction provides access to chiral synthons, which have proven useful for the construction of many structurally complex and biologically active compounds. Catalysis of these reactions is especially attractive with respect to avoiding the cost and relative chemical inefficiency associated with the use of chiral auxiliaries. 

Because unsaturated lactones and lactams are of importance as biologically active compounds, the carbonylative cyclization of alkynyl alcohols, alkynyl amines, and their allenyl derivatives has been extensively studied using various transition-metal complexes. Takahashi et al. [35] reported that Ru3(CO)12 also catalyzes the cyclocarbonylation of allenyl alcohols to five- to eight-membered unsaturated lactones (Eq. 20). 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

Scheme 2. Optically active alcohols that can be used to synthesize biologically important chiral compounds [7c, 22].

The significance for industrial processes is clear. Scheme 2 shows several examples from a survey recently published by Noyori [7c] of optically active alcohols that can be used to synthesize biologically important chiral compounds below along with some of relevance to the pharmaceutical industry [22]. Pheromones constitute a particularly diverse family of chiral aliphatic alcohols [23]. 

Chiral alcohols are useful starting materials for the synthesis of various biologically active compounds. The need for enantiomerically pure drugs and agrochemicals has increased in recent years [13]. Derivatives of enantiopure 1-phenylethanol are important chiral building blocks, which can be used as synthetic intermediates for the production of pharmaceuticals, fine-chemicals agrochemicals, and natural products. In particular (R)-1-phenylethanol is in widespread use as an ophthalmic preservative, an inhibitor of cholesterol intestinal adsorption, a solvatochromic dye, a fragrance, and so on. 

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