5.6- Dideoxy derivative

Pedersen further studied the reactivity of the intermediates 48 under dissolving metal conditions and synthesized the 5,6-dehydro-5,6-dideoxy derivative 55 which was catalytically reduced to the 5,6-dideoxy compound 56. 

New derivatives of L-ascorbic acid have been synthesized including saccharoascorbic acid, 5-ketoascorbic acid, 2-phosphoric-ascorbic acid, 6-bromo-6-deoxyascorbic acid, 6-chloro-6-deoxyascorbic acid, the 5,6-dehydro-5,6-dideoxy derivative, the 4,5-dehydro-5-deoxy derivative, the 5,6-dideoxy derivative, and numerous nitrogen derivatives. 

Preparations of A-aminoepimines and their catalytic reduction by hydrazine over Raney nickel have been described by Paulsen and Stoye. Using 5,6-di-(9-mesyl derivatives of 1,2-isopropylidene-ot-D-gluco-, ot-D-allo-, and ot-D-gulofura-nose (410-412), and compound 419, reactions with anhydrous hydrazine afforded the corresponding A-aminoepimines 413-415, and 420, which were regioselectively transformed into 5-amino-5,6-dideoxy derivatives 416-418, and 421. 

Whereas 2-deoxy-fortimicin A has full antibacterial activity (205), and the 2-deoxy-3-demethoxy- derivative is even more active than fortimicin A (236), the 2,5-dideoxy derivative has poor activity, as do the 2-deoxy-2-chloro and the 2,5-dideoxy-4,5-dehydro derivatives. The 2-amino-3-0-demethyl-2-deoxy analogue has quite good activity (229). 

In view of the unexpected effects of the C-2 and C-3 substituents on the reaction of C-4 sulfonates, it is worthwhile to point out the observations made with some 2,3-dideoxy derivatives. Treatment of ethyl 2,3-dideoxy-4,6-di-0-methylsulfonyl-D-ert/ hro-hexopyranoside (40) with sodium iodide and acetone at 115°C. caused the displacement of the C-6 mesylate group selectively to give 41. Catalytic hydrogenation then gave the corresponding ethyl 4-0-methylsulfonyl-2,3,6-trideoxy- -D-en/ /iro-hexoside in good overall yield (83%) (72). 

The first reported use of the DPM rearrangement in natural product synthesis can be found in the synthesis of methyl chrysanthemate, 71, reported by Pattenden and Whybrow (Scheme 18)35. This is produced directly by photolysis of 1,4-diene 70. While it should be noted that this reaction gave 71 in only 12% yield, it did furnish the desired product in a single step, with the correct relative stereochemistry. Bullivant and Pattenden also used a DPM rearrangement to form an advanced intermediate in the synthesis of the dideoxy derivative of the sesquiterpene taylorione, 7436. Irradiation of 72 afforded 73 in 45% isolated yield this was then simply converted to 74 using standard transformations. 

In addition to these physical studies at the Bureau, Tipson was able to return to his synthetic interests, both alone and in collaboration with other staff members. He was especially pleased to prepare D-talose in crystalline form, an accomplishment that had eluded Emil Fischer. Pursuing his longstanding interest in the reaction of sulfonic esters with iodide and following an earlier observation that the tetratosyl ester of erythritol is converted into butadiene by the action of sodium iodide and zinc, he demonstrated (with A. Cohen) that nonterminal unsaturation may be conveniently introduced into alditol derivatives by reaction of contiguous secondary sulfonates with sodium iodide and zinc dust in boiling A.A-dimethylformamide. This Tipson-Cohen reaction subsequently proved of great utility in other hands for the conversion of more complex carbohydrate structures into vicinal dideoxy derivatives. 

Figure 16. Synthesis of 2-deoxy, 3-deoxy, and 23-dideoxy derivatives of a.a-trehalose.

Scheme 4. Conversion of benzophenone-capped cyclodextrin to dideoxy derivative.

The 2,5-diamino-2,5-dideoxy derivatives of l,4 3,6-dianhydro-D-mannitol and -D-glucitol gave, on deamination, the same product, namely, l,4 3,6-dianhydro-L-iditol, in unspecified yield.176 The product presumably arose from carbonium-ion intermediates, which reacted predominantly with solvent on the less hindered, exo sides of the V-shaped molecule. 

R. D. Guthrie and D. Murphy, Nitrogen-containing carbohydrate derivatives. Part IX. Synthesis of 2,3-diamino-2,3-dideoxy derivatives, J. Chem. Soc. p. 6956 (1965). 

Sulfonic esters of sugar alcohols often react similarly with ammonia thus, l,4 3,6-dianhydro-2,5-di-0-tosyl-D-mannitol and -sorbitol give326 the corresponding 2,5-diamino-2,5-dideoxy derivatives. However, 1,4 3,6-dianhydro-L-iditol affords326 a compound thought to be 1,4 3,6-dianhydro-2,5-dideoxy-2,5-imino-D-mannitol. 

Lithium chloride, preferably dissolved in absolute ethanol, has also been used306 419 420 for preparing alkyl chlorides. Dissolved in absolute ethanol-acetone (1 1, by vol.), it has recently414 found application with alditol sulfonates. Its action on l,4 3,6-dianhydro-2,5-di-0-mesyl-L-iditol, l,4 3,6-dianhydro-2,5-di-0-mesyl-D-mannitol, and l,4 3,6-dian-hydro-2,5-di-0-mesyl- (and -2,5-di-O-tosyl-) sorbitol resembles the action of sodium iodide on these compounds, i.e., the first displays no appreciable reaction, the second gives the 2,5-dichloro-2,5-dideoxy derivative, and the last two afford the respective monochloromonodeoxy-mono-O-sulfonyl derivatives. Treatment of l,4 3,6-dianhydro-2,5-di-0-mesyl-sorbitol during 48 hours at 180-90° gives some of a dianhydro-mono-chloromonodeoxy-sorbitoleen. 

Different protecting groups such as acetonides, /-butyl dimethyl silyl derivatives proved to be stable under these experimental conditions, but the benzylidene group is completely cleaved.. The rate of photodeoxygenation is greater at the secondary positions [82], as indicated in Scheme 43, with the regioselective photolysis of dipivaloate to give a mixture of monodeoxy and dideoxy derivatives (81) in low yields. 

For the synthesis of the D-C portion, two different concepts were followed either by modification of laminaribiose (166) [89] or by a stereospecific P, 1 ->3-glycosylation [20]. Laminaran is isolated from seaweeds or from Poria cocos Wolf, degraded by selective acetolysis, and the lower oligomers separated by preparative HPLC [90]. Following acetylation, the heptaacetyl laminaribiosyl bromide is prepared and transformed into the disaccharide glycal 167 by the classical approach in 93 % yield. The 2-deoxy-2-iodo-a-glycoside is formed by application of the NIS procedure after deprotection and subsequent 4,6-0-benzylidenation, the precursor 168 for the radical formation of the 6,6 -dibromo-6,6 -dideoxy derivative is at hand. This compound may be further reduced to methyl-3-0-(P-D-chinovosyl)-a-D-olivoside (169). 

It appears probable that the aldimine II, initially formed by hydrogenation of the nitrile group, is itself in the stabilized, cyclic-hemiacetal form as a 1,2-diamino-l, 2-dideoxy derivative (III), the 1-amino group of which is subsequently hydrolyzed to yield the cyclic 2-amino-2-deoxy sugar (IV) directly.10 10a... 

Because there is only a small amount of dideoxynucleotide present, it is incorporated only occasionally. However, wherever it is incorporated into the growing piece of DNA, the polymerization is terminated because there is no 3 -hydroxy group to which the next nucleotide can be attached. This results in a series of DNA fragments of different lengths, each terminated at the base that was added as its dideoxy derivative. The synthesis of DNA fragments using dideoxycytosine triphosphate is outlined in Figure 27.5. 

Some of these reactions can also be used for non-radioactive labelling (Isaac 1994) since Tag-polymerase, DNA polymerase I and also terminal transferase can accept compounds such as digoxygenin-dUTP (DIG-dUTP) and the dideoxy derivative DIG-ddUTP as substrates. DIG-labelled DNA can be detected colorimetrically by antibodies coupled to peroxidase using chromogenic substrates. Similar procedures can also be used to label RNA using DIG-UTP with T7- or SP6-RNA polymerases. Digoxygenin labelling kits are commercially available. 

The deamination of the 2,5-diamino-l, 4 3,6-dianhydro-2,5-dideoxy derivatives of L-iditol and of D-glucitol has been observed to yield some 1,4 3,6- dianhydro-L-iditol in each case. The reactions evidently follow the SnI mechanism often observed in deaminations of simple aliphatic amines, and afford the product of the most stable type, with two exo hydroxyl groups. 

Boron trifluoride etherate [615-617] and SnCU [618,619] are the catalysts that are traditionally used in this reaction. Recently described promoters include IDCP [620,621], DDQ [622], montmorillonite K-10 [623], h [624], FeCls [625], InCls [626,627], Sc(OXf)3 [628], the l2-thiolacetic acid system [155], Yb(OTf)3 [629], and TMSOTf [630]. The 2,3-unsaturated glycosides produced in these reactions can easily be converted into the 2,3-dideoxy derivatives or to a variety of other products by functionalization of the double bond. 

Bozo, E, Boros, S, Kuszmann, J, Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-D-ribopyranosides as well as their 2-deoxy and 2,3-dideoxy derivatives possessing antithrombotic activity, Carbohydr. Res., 321, 52-66, 1999. 

The course of the acetylation of 6 was examined kinetically.684 The observed time-dependence of the total rate-constant was interpreted in the form of three independent, acetylation stages, for each of which the values of activation energies were determined the energy of the second stage685 is lower than those of the other two.688 The rate constants for all six dideoxy derivatives of l,6-anhydro-)8-D-hexopyran-oses during esterification with acetic anhydride in pyridine were estimated because of the known difference in the behavior of carboxylic acid anhydrides and the corresponding acid chlorides during esterification in pyridine, the reaction with acetyl chloride was also studied.408 The sequence of reactivities for acetic anhydride is... 

Ammonolysis of l,6 3,4-dianhydro-2-0-benzyl-/3-D-galactopyran-ose (188) affords the 4-amino-4-deoxy derivative.740 It was also used for the preparation of the 2-amino-4-fluoro- and 4-amino-2-fluoro-2,4-dideoxy derivatives of l,6-anhydro-/3-D-glucopyranose.381 The oxirane ring of most dianhydrides is readily split not only by ammonia but also by its derivatives, such as methylamine, dimethylamine,320,7 7 and benzylamine.635... 

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