Mannitol, structure

The inner etherification induced in the sorbitol and D-mannitol structures during polyester formation, made a study of their inner ethers or anhydrides a matter of practical significance. A new monoanhydride of sorbitol was described (21) and designated arlitan (from the initials of the Atlas Research Laboratory). Identification as 1,4-anhydro-D-glucitol was made by comparison of its sirupy tetramethyl ether with that obtained by acid anhydrization of Irvine s 2,3,5,6-tetramethyl-D-glu-citoP by oxidation of the tetramethyl ether to dimethyl-L-threaric acid [0-dimethyl-L-((iea tartaric acid] and identification as the crystalline diamide and by its behavior on oxidation with lead tetraacetate. ... 

Brigl and Grtiner reported another dibenzoyl-anhydro-D-mannitol (from the above-described reaction) which was shown (23) to be 1,4-anhy-dro-D-mannitol 2,6(or 3,6)-dibenzoate. Saponification yielded a crystalline anhydro-D-mannitol (n-mannitan) which was identical with that described previously by Valentin. The 1,4-anhydro-D-mannitol structure was established by the method of synthesis employed by Valentin ... 

A detailed spectroscopic and theoretical study of the conformation of dioxolanes 1 has appeared <96T8275>, and a theoretical study has shown that the anomeric effect explains the non-planarity of 1,3-dioxole <96JA9850>. The tetraalkynyldioxolanone 2 has been prepared and its structure and reactivity studied <96HCA634>. Both enantiomers of the chiral glycolic acid equivalent 3 can be prepared from D-mannitol <96HCA1696>, and lipase-mediated kinetic... 

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. 

Cobalt-on-alumina catalysts with increased dispersion and catalytic activity are prepared by addition of mannitol to the cobalt nitrate solution prior to impregnation. Thermogravimetric analysis (TGA) and in situ visible microscopy of the impregnation solution show that the organic compound reacts with cobalt nitrate, forming a foam. The foam forms because significant amounts of gas are released through a viscous liquid. The structure of the foam is retained in the final calcined product. It is this effect that is responsible for the increased dispersion. 

FIGURE 1.1 Structures of organic compounds referred to in the text (a) sucrose (also known as saccharose), (b) dimethyl sulfoxide (DMSO), (c) dimethylformamide (DMF), (d) sorbitol, (e) mannitol, (f) nitrilotriacetic acid (NTA), (g) citric acid, (h) N,N,N, N -fran,s-1,2-diaminocyclohexane-tetraacetic acid (CyTA), (i) saccharic acid, (j) glutamic acid. 

As described above, understanding the mechanism of the dispersion increase is a difficult task. In this work we compare a catalyst prepared by cobalt nitrate impregnation onto alumina with one modified by the addition of mannitol, and use TGA and in situ microscopy to investigate the increased dispersion. Mannitol is a sugar alcohol that is structurally similar to sorbitol [31], as shown in Figure 1.1. 

Enbrel is a product now approved for medical use that is based upon this strategy. The product is an engineered hybrid protein consisting of the extracellular domain of the TNF p75 receptor fused directly to the Fc (constant) region of human IgG (see Box 13.2 for a discussion of antibody structure) The product is expressed in a CHO cell line from which it is excreted as a dimeric soluble protein of approximately 150 kDa. After purification and excipient addition (mannitol, sucrose and trometamol), the product is freeze-dried. It is indicated for the treatment of rheumatoid arthritis and is usually administered as a twice-weekly s.c. injection of 25 mg product reconstituted in WFI. Enbrel functions as a competitive inhibitor of TNF, a major pro-inflammatory cytokine. Binding of TNF to Enbrel prevents it from binding to its true cell surface receptors. The antibody Fc component of the hybrid protein confers an extended serum half-life on the product, increasing it by fivefold relative to the soluble TNF receptor portion alone. 

Brigl and Griiner45 reported the isolation of three products when 1,6-di-O-benzoyl-D-mannitol (29) was heated in boiling 1,1,2,2-tet-rachloroethane in the presence of p-toluenesulfonic acid as the catalyst. These compounds were assigned mono- and di-anhydro structures, and were later shown by Hockett and coworkers46,47 to be 1,4-anhydro-D-mannitol dibenzoate (30), l,4 3,6-dianhydro-D-man-nitol dibenzoate (31), and 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol (32). The latter compound, which can be readily isolated from the... 

Ring contraction ofglycals.1 The oxidative ring contraction of cyclic alkenes (4,492-493) can be applied to protected glycals. Thus oxidation of the D-glucal 1 with TTN in CH3CN provides the 2,5-anhydro-D-manose 2, whose structure was established by conversion to the 2,5-anhydro-D-mannitol derivative (3). 

Dianhydro-n-mannitol or isomannide was first prepared many years ago by Fauconnier44 who obtained it by heating D-mannitol with hydrochloric acid. The dianhydrides of D-sorbitol and L-iditol were not prepared, however, until very recent times. Although isomannide is a crystalline substance forming well defined derivatives very little work has been carried out on it and its structure was not determined until 1945, but in that and the following years a flood of experiments having a... 

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