Synthesis from 2-deoxy-D-ribose

Radical-mediated deiodination, methanolysis of the acetate and subsequent oxidation of the resulting alcohol furnished the ketone 43 in 87% total yield. Transformation of 43 into the corresponding cyanohydrin acetate under ordinary conditions resulted in the formation of a diastereomeric mixture 44 and 45. However, only the kinetically favored cyanohydrin acetate 44 was obtained when treated with hydrogen cyanide and pyridine. Treatment of the nitrile 44 with HCl gas afforded the amide 46, which was subjected to alkaline hydrolysis followed by esterification of the resulting carboxyhc acid with diazomethane to furnish 5 in 11% overall yield from 27. 

Tamaoki, T. Nomoto, H. Takahashi, I. Kato, Y Morimoto,M. Tomita, F.Biocli m. Biophys. Res. Commun. 135 (1986) 397. 

Funato, N. Takayanagi, H. Konda, Y Toda, Y Hariyage, Y Iwai, Y Omura, S. Tetrahedron Lett. 35 

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The predecessor of Ultraflne was the Fine Chemicals Unit of Salford University Industrial Centre, which was set up partly to exploit a new route to prostaglandins.9 When the independent company was founded, it made sense to offer other eicosanoids. A key intermediate for the synthesis of leukotriene A4 (LTA4) (7), and thence LTC4, LTD4, and LTE4, was the epoxyalcohol (10), whose synthesis from 2-deoxy-D-ribose (8) (Scheme 29.2) had been reported.10... 

Deoxy-sugars. Part II. Synthesis of 2-Deoxy-D-ribose and 3-Deoxy-D-xylose from D-Arabinose, P. W. Kent, M. Stacey, and L. F. Wiggins,/. Chem. Soc., (1949) 1232-1235. 

Takahashi and coworkers have used INOC for synthesis of the chiral CD rings paclitaxel, which is an antitumor agent. Synthetic strategy starting from 2-deoxy-D-ribose is demonstrated in Scheme 8.22.110 The precursor of INOC was prepared by 1,2-addition of a,(3-unsaturated ester to ketone. INOC and subsequent reductive cleavage by H2/Raney Ni afford the desired CD ring structure. 

The Wittig reaction and its numerous derivations have undoubtedly proven to be one of the most useful and efficient methods for forming carbon-carbon double bonds . The reaction of an organophosphorus reagent with an aldehyde or ketone has also been frequently employed to extend simple dienals and dienones into more elaborate polyene systems. A key step in the convergent synthesis of the TB DMS-protected leukotriene A4 methyl ester, 19/ ,5 -Z-butyldimethylsiloxy-5S, 6S -epoxyeicosa-7 ,9 , 1IZ, 14Z-tetraenoate (43), was accomplished using a Wittig reaction between homoallylic phosphorus ylide 44 and Cl—Cll chiral epoxy dienal 45, derived from (—)-2-deoxy-D-ribose, shown in equation 29. ... 

Scheme 2.18. Synthesis of LTA4 and its optical isomers from 2-deoxy-D-ribose.

The Merck Frosst solution employed L-arabinose as a starting material, which was converted to the protected differentiated dialdehyde synthon 60 which functionally serves as a masked (7 )-2-OH-succinaldehyde. The protected hydroxyl is the future 12(/ )-hydroxyl in LTB4. Scheme 2.20 describes the synthesis of 63, the left part of LTB4, This intermediate is elaborated in several steps to phosphonium salt 64, which is then coupled to chiral aldehyde 68b, which comes from 2-deoxy-D-ribose following the route shown in the same scheme. Aldehyde synthon 68 contains the (5S)-protected hydroxyl necessary for LTB4. The asterisks indicated in the scheme for L-arabinose and 2-deoxy-D-ribose correspond to the stereocenters retained in intermediates 63 and 68, respectively. 

More recently, Rokach and Zamboni have reported the first stereospecific total synthesis of both the natural (5S)- and unnatural (5/ )-isomers of the 5-HETEs. The key to these syntheses, outlined in Schemes 3.3 and 3.4 was the use of the two enantiomeric aldehydes, (S)-21b and (/ )-21b, containing the asymmetric center which becomes C-5in the final products. The detailed synthesis of these key intermediates, both obtained from 2-deoxy-D-ribose, will be presented fully in Section 3.B... 

The (S)-isomer of the title compound has been used as a synthon in all but one of the reported syntheses of LTB4 as well as the synthesis of LTBx and a synthesis of (5/ )- and (5S)-HETE, as discussed above in Section 3.A.2. Corey s group has described two syntheses of the methyl ester (S) 21a, both starting from 2-deoxy-D-ribose. In path (Scheme 3.7), 2-deoxy-D-ribose was first protected as the acetonide, which was transformed to the epoxide 18. The latter was also obtained in a second synthesis (path B), which bypassed the initial protection of 2-deoxy-D-ribose as an acetonide. 

Drawing on experience from their work on the synthesis of LTA4 (to be described in Section 3.C) the Merck Frosst group also developed a synthesis of the ethyl ester (S)-21b from 2-deoxy-D-ribose (Scheme 3.8). The intermediate acetonide 22 served to protect the terminal diol unit and allow benzoylation to be effected on the desired hydroxyl group, thus serving the same protective purpose as the terminal epoxide in 18 (Scheme 3.7). But in addition, the acetonide 22 also served as a common intermediate to obtain the (7 )-isomer of 21b used in the synthesis of (52 )-HETE, as shown previously in Scheme 3.4. 

A stereoselective synthesis of 5(5),6(7 ),15(5)-trihydroxy-20 4(7 ,9 ,l 1Z,13 ) from D-xylose using zinc-mediated deoxygenation of the 4-hydroxy-2-butenoic acid moiety and base- induced double elimination of 4,5-epoxy allyl chloride as key steps was reported (44). The enantiomers R)- and (5)-3-hydroxy-20 4(5Z,8Z,llZ,14Z) were synthesized from coupling of a chiral aldehyde intermediate with a Wittig salt, which were derived from 2-deoxy-D-ribose and arachidonic acid, respectively (45). 

The chiral pool approach for the synthesis of enantiomerically pure compounds uses readily available sources of enantiomerically pure starting materials, usually naturally obtained. The most common sources are amino acids, monosaccharides and terpenes. Using this approach a number of structurally diverse enantiomerically pure compounds have been synthesised by carrying out a series of chemical transformations which will preserve the chiral information. There are both simple and more complex examples of this approach. For example, the insect pheromone (/ )-sulcatol (3) and the more complex fragment of brevetoxin B (2) are both prepared from 2-deoxy-D-ribose (Scheme 4.1) [2, 3]. 

Interestingly, both researches employed the same technique to install the methyl tetronate ring, that is, addition of the lithium anion of 4-methoxy-3-methyl-2(5H)-furanone to an aldehyde (106 or 113), but Kende used a TfjO-mediated dehydration to finish the synthesis, whereas Overman obtained the final structures after a Corey-Winter reaction to form the dialkoxy alkene unit (Scheme 1.16). In 2012, Martin et al. [77] managed to prepare enantioselectively Overman s intermediate 113 by an elegant cascade of reactions that culminates in the intramolecular dipolar cycloaddition of 119, prepared from 2-deoxy-D-ribose (120) (Scheme 1.16). 

A further signiHcant advance in Nicolaou s work on brevetoxin synthesis comes with the synthesis of the FGHU framework of brevetoxin A from 2-deoxy-D-ribose, D-glucal, and the known mannose-derived C-glycoside (65), as outlined in Scheme 14, the other chiral centres in (66) being derived from asymmetric epoxidation. O in model work on brevetoxin... 

Guindon et al. have reported a total synthesis of optically active leukotriene Bi (325). The key step in the synthesis was the base-catalysed opening of the tetrahydrofuran (323), obtained from 2-deoxy-D-ribose, to give the triene (324). 

What are the facts of life One of the most striking is that all known living systems involve the same types of polymers, i.e., three varieties of homochiral biopolymers. That is, each variety is composed of unique molecular building blocks having the same three-dimensional handedness. Thus, with rare exceptions, the proteins found in cells are composed exclusively of the 1-enantiomers of 19 optically active amino acids (Fig. 11.1). Similarly, only D-ribose and 2-deoxy-D-ribose sugars are found in the nucleic acid polymers that make up the RNAs and DNAs, which are essential for protein synthesis in the cell and for the transmission of genetic information from one generation to the next. 

Functionally and mechanistically reminiscent of the pyruvate lyases, the 2-deoxy-D-ribose 5-phosphate (121) aldolase (RibA EC 4.1.2.4) [363] is involved in the deoxynucleotide metabolism where it catalyzes the addition of acetaldehyde (122) to D-glyceraldehyde 3-phosphate (12) via the transient formation of a lysine Schiff base intermediate (class I). Hence, it is a unique aldolase in that it uses two aldehydic substrates both as the aldol donor and acceptor components. RibA enzymes from several microbial and animal sources have been purified [363-365], and those from Lactobacillus plantarum and E. coli could be induced to crystallization [365-367]. In addition, the E. coli RibA has been cloned [368] and overexpressed. It has a usefully high specific activity [369] of 58 Umg-1 and high affinity for acetaldehyde as the natural aldol donor component (Km = 1.7 mM) [370]. The equilibrium constant for the formation of 121 of 2 x 10M does not strongly favor synthesis. Interestingly, the enzyme s relaxed acceptor specificity allows for substitution of both cosubstrates propional-dehyde 111, acetone 123, or fluoroacetone 124 can replace 122 as the donor [370,371], and a number of aldehydes up to a chain length of 4 non-hydrogen atoms are tolerated as the acceptor moiety (Table 6). 

To date, 2-deoxy-D-ribose 5-phosphate aldolase (DERA) is the only acetaldehyde-dependent aldolase being applied in organic synthesis. Thus the stereoselectivity of DERA is significant, all known enzymes from different organisms showing the same preferences, limiting the field of application to syntheses in which specifically the DERA-catalyzed enantiomer is needed. 

Nicolaou and co-workers synthesized 1 from the simple starting material 2-deoxy-D-ribose in 83 steps. The overall yield of the synthesis was 0.043%, but the average yield for each site was about 91% (Nicolaou and Sorensen 1996). 

In the second synthesis from the Merck Frosst group,2-deoxy-D-ribose was used to obtain the C-glycoside 29 as described previously in Scheme 3.12. The key to the C-glycoside synthesis was the finding that with a suitable located leaving group, these structures open upon base treatment, as illustrated in... 

The carbohydrate component of ribonucleic acid and, therefore, of the corresponding purine nucleosides was identified as a pentose by Hammar-sten and, later, as D-ribose by degradation and then by synthesis. Because of the instability of 2-deoxy-D-erythro-peutose ( 2-deoxy-D-ribose ), its isolation from deoxyribonucleic acid was much more difficult. Levene and coworkers finally obtained the crystalline sugar from deoxyguanosine by brief treatment with dilute mineral acid. They established its identity by comparison with synthetic 2-deoxy-D-threo-pentose and 2-deoxy-L-er /[Pg.303]

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