Inosose formation

Quebrachitol was converted into iL-c/j/roinositol (105). Exhaustive O-isopropylidenation of 105 with 2,2-dimethoxypropane, selective removal of the 3,4-0-protective group, and preferential 3-0-benzylation gave compound 106. Oxidation of 106 with dimethyl sulfoxide-oxalyl chloride provided the inosose 107. Wittig reaction of 107 with methyl(triphenyl)phos-phonium bromide and butyllithium, and subsequent hydroboration and oxidation furnished compound 108. A series of reactions, namely, protection of the primary hydroxyl group, 0-debenzylation, formation of A-methyl dithiocarbonate, deoxygenation with tributyltin hydride, and removal of the protective groups, converted 108 into 7. 

A more unusual monoepoxidation was observed when l-halo-l,3-cyclohexadienes were treated with aqueous solutions of potassium permangnate35. Oxidation of 18 resulted in formation of the unusual halo-epoxydiol 19 as the major oxidation product (equation 19). Hydrolysis of 19 with water in the presence of AI2O3 afforded the rare inosose 20 in high yield. 

The General myo-lnositol and scyllo-Inosamine Pathway. Two distinct cyclitol pathways, which we earlier called Ca (started by myo-inositolphos-phate synthase) and Cb (started by T-deoxy-i cy/to-inosose synthase), are used in the initiation of AGA pathways. Here we will describe the Ca route and the Cb pathway in the paragraph on NEOs (see Section 2.2.2.1.3). The cyclitol pathway in the biosynthetic pathways for STRs, but also for other AGAs such as SPCs, KAS, and FORs and also the mixed type antibiotic HYG-A (see Section 2.2.4.3.1), starts with the formation of myo-inositol in a two-step pathway (Ca) that is not encoded in the itrAtt-clusters. The first step in streptidine biosynthesis (and any other myo-inositol utilising pathway) is the formation of a myo-inositol monophosphate (D-myo-inositol-3-phosphate or L-myo-inositol-1-phosphate) via L-myo-inositol-1-phosphate synthase, which in actinomycetes... 

Formation of the Initial Cyclitol. The first steps of FOR production are the same as in the biosynthesis of STR in short, the first step in FOR biosynthesis is postulated to be the formation of a myo-inositol monophosphate (D-myo-inositol-3-phosphate or L-myo-inositol-1-phosphate) via the cellular l-myo-inositol-1-phosphate synthase as in the STR pathway (Ca pathway see Section 2.2.1.2). As in the itr-Att-clusters, no gene for this enzyme has been found in the/or-cluster. As a second step in FOR biosynthesis the dephosphorylation of D-myo-inositol-3-phosphate via an inositolmonophosphate phosphatase has to follow. A putative gene product with this activity is that of the ForA protein (cf. Tables 2.17 and 2.18). The cyclitol is postulated to be first converted via two enzymes, a cluster-encoded myo-inositol 3-dehydrogenase (ForG member of the GFO/IDH/MocA oxidoreductase family) and the L-glutamine icy//o-3-inosose 3-aminotransferase (ketocyclitol aminotransferase I ForS), to icy//o-inosamine (3-deoxy-3-amino- cy/to-mositol). 

Reactions of the carbonyl group of inososes include the addition of diazoalkanes, dithioacetal formation, reduction, hydrogenolysis, and phenyl-hydrazone formation. The epoxide CXXX, which is formed from scyllo-inosose pentaacetate and diazomethane, is the starting material for a considerable series of seven-carbon derivatives.1 Some of the newer compounds of this group are discussed on pages 187 and 188. 

When the hydrogen transferred as hydride to the cofactor is retransferred to the same carbon atom in the product, the movement is far more difficult to detect. The conversion of D-glucose 6-phosphate (58) into lL-mt/o-inositol 1-phosphate (61) occurs by cyclization of the carbon skeleton, with formation of a new bond between C-l and C-6. When each carbon atom in turn was specifically labeled with tritium, there was complete retention of tritium, even in the presence of added NADH, although there was an apparent, small isotope-effect with D-glucose-5-t 6-phosphate.19 The mechanism proposed for the cyclization19 was an initial oxidation at C-5 to give NADH and xylo-hexos-5-ulose 6-phosphate (59), followed by an aldol reaction causing cyclization to lL-myo-inosose-2 1-phosphate (60), which is then... 

The question of the configuration of epi-meso-inosose has recently been answered by Posternak. Examination of the formula for meso-inositol (V) will reveal that oxidation might give rise to six inososes. Attack at the equivalent positions one and three would give the enantio-morphous pair of inososes (XXXIII and XXXIV). In precisely the same manner, oxidation of carbons four and six would give the enantio-morphous pair XXXV and XXXVI. On the other hand, oxidation at either position two or five would result in the formation of the sym-... 

The basic permanganate oxidation of conjugated 1,3-dienes is different from those reported for the 1,4-dienes above. Therefore, in the oxidation of cyclopentadiene and 1,3-cyclohexadiene (13) a mixture of five products 14-18 is obtained (equation 4) . In this reaction 14 and 16 are derived from the normal cis hydroxy la tions whereas 17 and 18 were said to be formed from 15 by hydration in what the authors term an epoxidic pathway. Formation of epoxy-diols under similar permanganate oxidations has been found for occidentalol (19), levopimaric acid (20) and a 1-chloro- or 1-bromo-l,3-diene (21) as an intermediate step in the synthesis of (+)-D-c/tfrc-3-inosose and (+)-D-c/r/ro-3-inositol (equation 5). The explanation for the epoxide formation in the oxidation of 1,3-dienes (13, 19-21) is not clear but may be connected to the fact that other additions of permanganate to dienes are possible beyond those commonly observed... 

The catalytic oxidation of inositols having three axial hydroxyl groups leads again to the formation of monoketones only. Again, the reaction is remarkably selective. Angyal oxidized muco-inositol (50) to the inosose... 

O i) Formation of Stable Free-Radicals.—The ESR probe can be used to distinguish between the hydrazine derivatives of saccharides and nonsaccharides. Saccharide phenylhydrazones, which are much less stable in basic media than inosose ph enylhydrazon es, exhibit 3-linc ESR patterns... 

The pyranoid conformations of the amino-deoxyoctoses (6) and (7) have been calculated using modified Karplus equations. Enediol anion formation in inososes has been studied by u.v. and n.m.r. spectroscopy. The results suggested that the interpretation of n.m.r. data by Dufaye (Appl. Polym. Symp., 1976, 28, 955) was erroneous and that only small concentrations of enediolate ions are formed. 

Figure 34 The wo general routes to the formation of faminoOcyclitols. (A) The Cal pathway via D-myo-inositol-J-phosphate synthase (mlPS). (B) The Cbl pathway via the dehydroquiruite synthaselike enzyme 2-deoxy-scyUo-inosose synthase (2DOslS). For the introduction of a fint amino-group in the cyclitol in Cal, a de(dsosphoryiation fmlPP), a dehydrogenation (tnlDH), and a transamination (TA) step have to follow, whereas in the Cbl route transamination is possible directly. For details see Refs. 5,8,94, and 99.

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