Mannitol ring opening

Deoxy-4-fluoro-D-fructose (552) was prepared (59%) by fermentation of 3-deoxy-3-fluoro-D-mannitol with Gluconobacter oxydans. The structure of 552 (fi-T) form) was confirmed by the n.m.r. spectrum, which resembles that of 4-deoxy-4-fluoro-Q -D-sorbopyranose (553) 552 was identical with one of the products obtained from the oxirane-ring opening of 3,4-anhy-dro-l,2-0-isopropylidene- -D-tagatopyranose with KHFj. 

Guan et al. have recently published the preparation of galactitol and D-mannitol-derived permethylated polyesters 62 [41] and the living ring-opening polymerization of the galactonolactone 20 [42] giving polyester 63. The latter exhibited protein resistance. 

In the alditol series, examples of acetobrominolysis of O-isopropyl-idene groups of derivatives of D-mannitol and D-iditol were given by McCasland and coworkers.i . i i Thus, the D-mannitol trithioearbonate derivative 157 gave the 1,6-dibromo derivative 158 (yield 55%).160 The same bromation with ring-opening was described for the D-iditol tri-thiocarbonate analog (yield 77%). 

Epoxide-ring opening of 5,6-anhydro-l,2 3,4-di-0-isopropylidene-D-mannitol (228) occurs under relatively mild conditions with potassium... 

Scheme 6.42, diisopropylidene mannitol was treated with A, A -dimethylformamide dimethyl acetal followed by methyl iodide to effect this transformation [74,75]. The reaction proceeds through initial acetal transfer generating the illustrated mannitol acetal. Methyl iodide then alkylates the nitrogen, producing a quaternary ammonium salt. Loss of trimethylamine, followed by ring opening and decomposition, gives the 3,4-olefinic mannitol derivative shown. 

Various protected bicyclic 2,5-anhydro derivatives of 5-thio-D-mannitol were obtained from methyl 2,3,4-tri-(9-acetyl-6-(9-mesyl-5-thio-a-D-glucopyranoside by transannular participation of the ring sulfur atom and ring opening of the thiiranium ion [35]. Similar reactions were earlier observed with, for example, a 4-(9-methanesulfony 1-5-thio-D-xylopyranose [36]. 

A synthesis of 3 starting from a conformationally flexible D-mannitol A-Boc bis-aziridine derivative 81 has been reported (Scheme 14). The cyclic carbamate-protected pyrrolidine 82 was obtained from 81 via the regioselective bis-aziridine ring opening with Li2NiBr4, followed by Ag+-promoted intramolecular substitution of the bromide by the N -Boc group in 75% overall yield. Nitrous acid deamination of 82 with isoamyl nitrite led, in 50% yield, to a 1 1 mixture of cyclic carbamate protected pyrrolidines 84 and 85 via the intermediate... 

The ring opening/ring closure of bis epoxides with amines offers a route to polyhydroxylated azepines. The formal reaction is shown in Scheme 5 and this method has been applied to the preparation of enantiopure azasugars derived from Z)-mannitol and L-iditol <94TL3293>. The ratio of 6-exo-tet cyclisation to 1-endo-tet cyclisation may be controlled by modification of the reaction conditions. 

Another study pertinent to the present discussion is that of the acid-catalyzed dehydration of tetratols, pentitols, and hexitols, all of which yield tetrahydrofuran derivatives as the primary products. These reactions are first order with respect to the alcohol and the acidity function Hq, and the direct relationship shown from plots of versus Hq implies that the reaction proceeds via a protonated intermediate.In all cases except one, the major cyclic product is derived from HO-5 displacement of water from C-1. The exception is D-mannitol (213), where HO-3 participation leads to a slight preference for formation of 2,5-anhydro-D-glucitol (214) over 1,4-anhydro-D-mannitol (215). Inversion at C-2 occurs with HO-5 participation during ring opening of the epoxide (214). 

D-Mannitol as reagent 17, 201 Marasse s. Kolbe-Schmitt Marckwald furan ring opening 7, 191 10, 136... 

Cope and Shen58 observed that, when a solution of 1,4 2,5 3,6-trianhydro-D-mannitol in concentrated hydrochloric acid is heated on a steam-bath, the 1,4- and 3,6-rings are opened, affording 2,5-anhydro-l,6-dichloro-l,6-dideoxy-D-mannitol in good yield. 

The three l,4 3,6-dianhydrohexitols show the shielding effect of the cts-fused oxolane ring on their di-O-sulfonyl derivatives. As C-2 and C-5 of 1,4 3,6-dianhydro-D-mannitol 2,5-di-p-toluene-sulfonate and 2,5-dimethanesulfonate are open to attack from the exo direction, they react readily with such nucleophilic reagents as benzoate in /V,iV-dimethylfoimainide,94 acetate in acetone,93 thioacetate,95 phthalimide in A/,JV-dimethylformamide,93 and iodide in acetic anhy-dride.59<6) Inversion occurs at these positions and the L-iditol configuration results, as pointed out in the several examples in Table V. However, hydroxide ion may merely saponify,92 with retention of configuration.93... 

Diols and polyols can participate in equilibria with boric acid in aqueous solution. The stability of polyolborates is determined by the number of OH groups in cis positions. Complexes with polyols are more stable than with diols, and 1,2-diol complexes are more stable than their 1,3-diol counterparts (Table 10) since the resulting five-membered chelate ring is unstrained.75120 In the case of 1,3,5-triols stable cage-like structures (5) and (6) are favored. Open-chain or five-membered cyclic polyols form more stable chelate complexes than their six-membered counterparts.120 Thus, chelates from alditols and ketohexoses are more stable than the corresponding aldose chelates (Table 10). Many polyols allow quantitative titrimetric determination of boric acid. Of these, mannitol remains the most widely used reagent on the basis of availability, cost and ease of handling.75... 

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