Mannitol, compounds available from

Scheme 5. Compounds available from bisdeoxygenation of mannitol or...

A chemo- and diastereoselective carboityl addition reaction and standard manipulations could be used to fashion compound 26 from ketone 27, a substance that can ultimately be traced retro-synthetically to enantiomerically pure 2-deoxy-D-ribose (29) (Scheme 2.3c). This doubly convergent approach reduces the synthetic problem to three readily available and enantiomerically pure building blocks, D-mannose (10), D-mannitol (18), and 2-deoxy-D-ribose (29). 

Recently a series of compounds resulting from the reaction of mannitol esters with a varying number of moles of ethylene oxide have been made available commercially. These compositions serve as dispersion agents. One of these, mannitan monolaurate which is combined with 20 moles of ethylene oxide is employed as a dispersing agent for volatile oils, oil-soluble vitamins and many other edible and drug products. This product is an oily liquid, miscible in all proportions with water and alcohol it is soluble in cotton seed oil and insoluble in ether. 

A similar Evans asymmetric aldol/reduction sequence could also serve well in a synthesis of fragment 158. Compounds 161 and 162 thus emerge as potential precursors to 158. In theory, building blocks 161 and 162 could be procured in optically active form from commercially available and enantiomerically pure (+)-/ -citro-nellene (163) and D-mannitol (164), respectively (see Scheme 42). 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

Optically pure glyceraldehyde acetonides are widely used in the synthesis of enantiomerically pure compounds (EPC synthesis).1 2 3 4 5 Whereas D-(R)-glyceraldehyde acetonide is easily obtained from the inexpensive D-mannitol,6 7 there are only a limited number of practical syntheses of the enantiomeric L-(S)-glyceraldehyde acetonide.8 9 Difficulties arise from different sources 1) availability of the starting material diisopropylidene-L-mannitol 2) length of the synthesis 10 3) nature of the reactants used mercury acetate, mercaptans, lead tetraacetate, ozone at -78°C, 4) moderate yields.11 14... 

Nature is the world-leading chemist in synthesizing chiral enantiopure substances, and a vast variety of structures isolated from plant or animal sources are available for the synthetic chemist to use as starting materials. Examples of chiral synthons from nature are amino acids, carbohydrates, hydroxy acids, terpenes, alkaloids, and so on (Figure 1.44). The most representative among them are commercially available compounds, such as ascorbic acid, (+)-calcium panthotenate, (—)-carvone, dextrose, ephedrine hydrochloride, (+)-limonene, L-lysine, mannitol, monosodium glutamate, norephedrine hydrochloride, quinidine, quinine, sorbitol, and L-treonine. The chiral pool strategy uses chiral compounds from nature or products derived thereof (e.g., from fermentation processes). Examples of industrial... 

The development of in vitro models for the BBB has enabled the study of transport phenomena at the molecular and cellular levels. The aim of such in vitro BBB models is to functionally resemble as many as possible the unique characteristics of the BBB. Compared with in vivo animal models, the in vitro models are relatively accessible, flexible, reproducible, and abundantly available. Previous investigations showed that the permeability of the in vitro BBB models to various compounds such as sucrose, retinoic acid, retinol, haloperidol, caffeine, and mannitol was comparable to the permeability data obtained from in vivo models [61]. 

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