Synthesis from D-mannitol

5-iV-benzylimino-l,3,4,6-tetra-0-benzyl-L-iditol (73). Hydrogenation of 73 removed the benzyl groups to give, after neutralization and purification by ion-exchange chromatography, 23 in 37% overall yield from 70. 

5-di- 9-mesylate derivative 76, which upon heating in benzylamine afforded the tetra-substituted pyrrolidine 79. Successive treatment of 79 with cone. HCl in methanol provided the A-benzyl-tetraol hydrochloride salt 80, which on hydrogenation produced 23. 

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McQuade et al. [11] have pubhshed a nice synthesis using a microencapsulated nickel-based catalyst for promoting a Henry reaction based upon the work of Evans [12]. Torrens et al. have pubhshed a somewhat longer synthesis from D-mannitol bisacetonide [13]. 

Mesembrine (-)-Mesembrine (12) is an octahydroindole alkaloid isolated from certain plants of the Sceletium genus, namely S. namaquense, S. strictum and S. tortuosum The mesembrine sttucture has been established as 12. Mesembrine was synthesized from noncarbohydrate, and its synthesis from D-mannitol has been presented herein. 

This procedure describes the preparation and use of an effective chiral catalyst for the asymmetric allylation of aldehydes. A previous synthesis of optically pure 1-(phenylmethoxy)-4-penten 2-ol requires seven steps from D-mannitol.4 This procedure has been employed successfully with other aldehydes,5 and also with methallyltributylstannane5 (see Table). Catalysts prepared from (R)- or (S)-BINOL and Ti(0-i-Pr)4 at 2 1 stoichiometry have also proven useful in these reactions.The olefinic products may be regarded as latent aldol products between aldehydes and the enolate of actetaldehyde or acetone. In all cases examined thus far, enantioselectivity... 

An alternative synthesis of lactone derivatives (178) from (D)-( + )-mannitol was also reported, c.f. ... 

A similar approach was used by Mihailovic and coworkers.16 When 2-te-trahydrofuranethanol (119) was treated with lead tetraacetate, an intramolecular ring-closure occurred, to give a 45% yield of (R, flJ-m-2,6-dioxabicy-clo[3.3.0]octane (115), together with seven other compounds in minor proportions. Compound 115 was prepared from D-mannitol by following the established procedure of Cope and Shen,193 and was used as an intermediate for the first synthesis of thiacyclodeca-4,7-diene.200 Finally, several... 

Three-step synthesis starting from D-mannitol... 

Ph Ph Epoxidation of aldehydes [6.8] Three-step synthesis starting from D-mannitol... 

An elegant stereospecific synthesis of (+)-muscarine (2 R = NMe3) has been achieved by reduction of the epoxide (1) (easily produced from D-mannitol) with sodium bis-(2-methoxyethoxy)aluminium hydride to give predominantly (2 R = OH) on monotosylation, this forms (2 R = OTs). Chromatographic resolution and treatment with trimethylamine yielded (-l-)-muscarine (2 R = NMea).1... 

The synthesis of 3-0-methyl-D-glyceraldehyde starts with D-fructose [52]. The preparation of 2-0-methyl-D-glyceraldehyde and 2-0-benzyl-D-glyceraldehyde (R)-25 starts from D-mannitol [53]. 

Depazay and co-workers have described the synthesis of a series of polyhydroxylated pyrrolidine, piperidine and azepanes derived from D-mannitol as novel mimetics of somatostatin [8]. The synthesis of one piperidine 116 is shown in O Scheme 9. The authors used reaction of tr) tamine with the D-mannitol derived bis-epoxide 112 followed by protection of the indole nitrogen with a Boc group to prepare the L-gulo-piperidine 113, the azepane 114 also being formed. Selective protection of the primary alcohol followed by reaction with hydrazoic acid... 

An alternative synthesis of synthon 62, Scheme 2.20, based on a yeast fermentation, has been described by Fuganti et al. and a versatile approach to a-benzoyloxy aldehydes from D-mannitol has given 62, R = benzoyl. 

Scheme 3.32. Synthesis of LTA4 intermediates from D-mannitol via D-glyceraldehyde.

A double nucleophilic attack by benzylamine on a symmetric bis-epoxide, prepared from D-mannitol, was used in a recent synthesis of 250 [564], In another recent report, 5-keto-D-glucose was reacted with diphenylmethylamine and sodium cyanoborohydride in a key step in the formation of 250 [565]. 

Alternatively, the synthesis of 23 from D-mannitol has been started by acetalation with benzaldehyde to give l,3 4,6-di-C -benzylidene-D-mannitol (74) (58%), which was tri-flated to form the ditriflate 75 (95%) (Scheme 13). Nucleophilic substitution of the ditriflate groups in 75 with anhydrous hydrazine afforded compound 77, which was hydrogenated over Raney nickel to give the protected pyrrolidine 78 (1(X)%), which upon acid hydrolysis gave 23. 

Synthesis from o-mannitol The alditols have been also utilized for the synthesis of such series of compounds. Thus, D-mannitol has been used for the synthesis of... 

Synthesis from o-mannitol The AB ring of sesbanimide was also synthesized from cyclohexyhdene D-glyceraldehyde 57, readily available from D-mannitol (Scheme 8). ° The addition of (Z)-7-alkoxyallylboronate 56, prepared from 55, to 57... 

Synthesis from o-mannitol Syntheses of (+)-30, 31 and (+)-31 from chiral 0-benzylglycidol (203), readily available from D-mannitol, have been achieved by... 

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