Proline analogs synthesis

Fluorous Synthesis of Biaryl-Subshtuted Proline Analogs. 112... 

Fluorous Synthesis of Biaryl-Substituted Proline Analogs... 

Fig. 30 Microwave-promoted fluorous synthesis of biaryl-subshtuted proline analogs. Reagents and condihons a EtaN, DMF, MW 150 °C, 15 min, 40-75%, closed vials b R""PhB(OH)2, Pd(dppf)Cl2, K3PO4, toluene Acetone H2O, MW 120 °C, 12 min, sealed vial system, 19-79%. R=Me, Et R = Me, 1 - Pr R" = H, 3-MeO R" =Me, Et R""= 4-MeO, 3-Cl, 4-Ac,3,4-diCl,3,4-methylenedioxy...

Proline analogs, biaryl-substituted, fluorous synthesis 112 PS-anthracene, dienophiles 151 PS-carbodiimide 136 Pimine C-2, nucleophilic displacement 119... 

The reaction also proceeds efficiently when smaller amounts of catalyst are used. For example, the analogous synthesis of 5a gave 92% yield and 84% ee in the presence of only 2 mol% L-proline (compared with 93% yield and 92% ee with 50 mol% catalyst) [7]. This reaction has already been performed on a gram scale. 

Synthesis of Unnatural (S)-Proline Derivatives. The condensation of pivaladehyde with (S)-proline yields stereoselec-tively, after lithiation and reaction with an electrophile, the hi-cyclic compound (28), which is a versatile educt for the synthesis of many a-suhstituted proline analogs (29) (eq 12). The reactions proceed via the formation of a chiral lithium enolate without the use of a chiral auxiliary (self-reproduction of chirality). The reaction with a variety of electrophiles cis to the t-Bu group yields a plethora of a-substituted (5)-proline derivatives (29). A limitation of this strategy is the acetal cleavage of some substituted products (28). ... 

Synthesis of enol triflate from N-acylated lactam has been reported. Comins synthesized (5)-pipecolic acid 33 (Scheme 19) from enol triflate 30 of piperidone derivative 29 by Pd-catalyzed carbonylation followed by aymmetric hydrogenation nsing a mthe-nium catalyst with (i )-BINAP. Preparation of the first enantiopure lactam-derived enol triflate from (5)-pyroglutamic acid was achieved, and the synthesis of a proline analog was obtained in good yield (86% de). ... 

Uitto, J., Hoffmann, H. P., and Prockop, D. J., 1976, Synthesis of elastin and procollagen by cells from embryonic aorta. Difference in the role of hydroxyproline and the effects of proline analogs on the secretion of the two proteins. Arch. Biochem. Biophys. 173 187-200. 

B. C. Hamper, D. R. Dukesherer, M. S. South, Sohd-phase synthesis of proline analogs vw a three component 1,3-dipolar cycloaddition. Tetrahedron Lett. 1996, 37, 3671-3674. 

Hampl996 Hamper, B.C., Dukesherer, D.R. and South, M.S., Solid-Phase Synthesis of Proline Analogs via a Three Component 1,3-Dipolar Cycloaddition, Tetrahedron Lett., 37 (1996) 3671-3674. 

The chemical method for the synthesis of P2 moiety suffers from at least 50% yield loss in the resolution process [164]. Biocatalytic desymmetrization of substituted pyrrolidines to give the desired enantiomer is an attractive approach to access proline analogs. 

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

Proline has been often used in reactions with aldehydes to form 1-oxo perhydropyrrolo[l,2-f]oxazole structures <1998J(P1)3777, 2004PNA5839>. These compounds were used for the asymmetric synthesis of proline derivatives which are present in natural products or analogs (Scheme 49) <2005T10018, 2005TA2075, 2006JOC97>. 

The synthesis of l-methylpyrrolizid-7-one49 was very important for final confirmation of the structure of the naturally occurring pyrrolizi-dine bases. The starting ethyl ester of 3-methylproline (80), obtained by analogy with proline,50 was condensed with ethyl acrylate and the condensation product (81) converted into l-methylpyrrolizidine-7-one (82) by cyclization and ketonic hydrolysis. A similar route starting with the ethyl ester of 3-methyl-L-proline afforded optically active... 

Analogous bicyclic products with different substitution patterns, e.g. 103 [116], were also synthesized (Scheme 6.46, Eq. 3). Compound 103, which is (in the same way as 96) also an intermediate in the synthesis of steroids, was prepared starting from 102 in the presence of one equivalent (S)-phenylalanine as catalyst [116]. The enantioselectivity of 76% ee was determined after derivatization into a known compound. It is worth noting that for preparation of 103 use of L-proline gave less satisfactory results. A graphical overview of synthesized bicyclic products (related to 96) with different substituted patterns is given in Scheme 6.46. 

Alsina, J., Scott, W. L., and O Donell, M. J., (2005) Solid-phase synthesis of a-substituted proline hydantoins and analogs. Tetrahedron Lett. 46, 3131-3135. 

Chiral Amines with C2 Symmetry, trans-2,5-Dimethylpyrrolidine (1) was the first chiral amine possessing C2 symmetry used as a chiral auxiliary in asymmetric synthesis. Since that time a number of related systems have been developed including the title compound (2) and (4). These amines were developed as C2-symmetric analogs to the commercially available prolinol derivative (5). While proline-derived chiral auxiliaries have been widely used in asymmetric synthesis, the C2-symmetric chiral auxiliaries often give enhanced stereoselectivity when compared directly to the prolinol derivatives. Unfortunately the preparation of the C2-symmetric compounds is more tedious and, at the time of writing, none are commercially available. For example, the standard route to chiral pyrrolidines (2) and (3) involves the resolution of tranf-N-benzylpyrrolidine-2,5-dicarboxylic acid, although other preparations have been... 

---