Trehaloses preparation

S. Hanessian and P. Lavallee, Selective substitution reactions of a,a-trehalose Preparation of 6-monofunctional derivatives, Carbohydr. Res. 38 303 (1973). 

Trehalose Standard Preparation Determine the water content of a Trehalose standard (available from Hayashibara International, Inc., Suite 200,8670 Wolff Court, Westminster, CO 80031-6953) as directed under Water Determination, Appendix IIB. Use the calculated dry weight as the value for 100% pure Trehalose. Prepare the Trehalose Standard Solution by dissolving 1 g of anhydrous Trehalose in sufficient water to bring the volume to 25 mL. 

Came and coworkers have described a toxic lipid extracted from Coryne-bacterium ovis, a pathogen which, in sheep, causes a wide-spread disease known as caseous lymphadenitis. The lipid extracted from living C. ovis with petroleum ether is toxic for leucocytes in vitro. A preliminary chemical investigation of this lipid fraction, kindly prepared by Dr. Came, has not yet yielded definite information about the chemical nature of the active fraction. A synthetic 6,6 -dicorynomycolate of trehalose, prepared by Diara and Pudles, has been found devoid of leucotoxic action. 

Recently, a Click polymerization strategy has been utilized to produce glycopolymers in which carbohydrates are incorporated into the backbone [198, 199]. Eissa and Khosravi demonstrated the copper wire-catalyzed Click polymerization of di-alkyne-terminated PEG with di-azide-functionalized trehalose prepared by tosylation/acetylation of a,a-D-trehalose followed by azidation reaction (Scheme 12) [199]. The produced alternating linear glycopolymers with triazole linkers were fully characterized and the polymer with a PEG segment of 600 gmol showed a lower critical solution temperature (LCST) at 39°C, which is known as the fever temperature. This material constituted a new class of temperature-responsive water-soluble glycopolymers. 

C-Disaccharide analogs of trehalose were recently [20c] prepared by using as a key step an aqueous Diels-Alder reaction between the sodium salt of glyoxylic acid and the water soluble homochiral glucopyranosil-l,3-pentadiene 19 (Equation 6.1). A mixture of four diastereoisomers in a 41 24 21 14 proportion was obtained after esterification with methanol and acetylation. The main diaster-eoisomer 20 was isolated and characterized as benzoyl-derivative. 

Online detection using 4H nuclear magnetic resonance (NMR) is a detection mode that has become increasingly practical. In a recent application, cell culture supernatant was monitored on-line with 1-dimensional NMR for trehalose, P-D-pyranose, P-D-furanose, succinate, acetate and uridine.33 In stopped-flow mode, column fractions can also be analyzed by 2-D NMR. Reaction products of the preparation of the neuromuscular blocking compound atracurium besylate were separated on chiral HPLC and detected by 4H NMR.34 Ten isomeric peaks were separated on a cellulose-based phase and identified by online NMR in stopped-flow mode. 

As shown in Eq. 12.54, with glyoxylate as the dienophile, if the attack is on the si face of the diene, it would lead to the skeleton of KDO if the attack is on the re face, it would lead to the skeleton of KDN. C-Disaccharide analogs of trehalose were prepared using an... 

Trehalose 6-phosphate has been prepared in 28% yield through unimolar phosphorylation of the disaccharide with diphenyl phos-... 

In addition to Bronsted acid promoted Fischer-type glycosylations, Lewis acids have been investigated (Scheme 3.4). A variety of Lewis acids promote glycosylation under mild conditions, often in substoichiometric amounts. The earliest examples include ZnCl2 [18] and FeCl3 [19], although these readions were demonstrated only for preparation of trehalose-type disaccharides. Mukaiyama et al. have very recently developed metal triflate catalysts for the dehydrative glycosylation with... 

Similarly, when the selective O-pivaloylation of trehalose was investigated by Richardson, Hough, and Cortes-Garcia, a number of useful derivatives were also obtained in quantities adequate to be of preparative value. Thus when 12 equivalents of pivaloyl chloride were employed for this esterification at — 20 °C, and the reactants were thereafter stored at room temperature for three days, a 61% yield of the 2,2 3,3, 4, 6,6 -heptapivalate was obtained, and following invertive chlorination with sulfuryl chloride, a displacement with different nucleophiles gave access to C-4-modified trehaloses, one example of which is shown in Scheme 17. 

Richardson s interest in these trehalose epoxides stemmed from his desire to prepare a wide range of modified trehalose analogues for evaluation as inhibitors of the trehalase of insects, as trehalose is known to be the storage carbohydrate of many insects and good inhibitors of this processing enzyme could potentially function as green insecticides. 

SCHEME 33. Fluoro-trehalose derivatives prepared by Hough, Richardson, and Hadfield (1978). 

Tonicity agents are added to injectable preparations to prevent osmotic shock at the site of injection upon administration, and thereby reduce local irritation. Typical excipients used for tonicity adjustment include saline, glycerin, mannitol, dextrose, and trehalose. Tonicity is a colligative property that depends primarily on the number of dissolved particles in solution. Hence, the amount of tonicity agent to be added depends on the specific formulation. Typically, osmolality of 280 to 320mOsm is considered iso-osmotic. 

Following the work of Mclnnes,289,290 methanolysis in the presence of potassium carbonate was used to prepare methyl 6-O-acetyl- and methyl 6-0-octadecanoyl-/3-D-glucopyranoside,291 o-nitrophenyl /3-D-galactopyranoside 6-phosphate,292 methyl 5-thio-a-D-glucopyranoside 6-phosphate,293 and 6,6 -di-0-hexadecanoyl-a,a-trehalose,294 from the appropriate, per-0-(trialkylsilyl)ated precursors. 

---