Synthesis allosamizoline

The phenylthionocarbonate procedure was also used for the cyclization of a 5-oxime-ether radical (Scheme 6) [17]. The stereochemical outcome of this reaction is almost identical with that observed for a closely related 6-methoxyhex-5-enyl radical cyclization [12,14]. A related glucosamine-derived radical cyclization has been employed for the synthesis of allosamizoline 13 [18]. Other examples in this area include the cyclization of... 

Clearly, in the Kuzuhara synthesis of (—)-allosamizoline, we have seen yet another powerful strategy for ring synthesis, namely ring-contraction, being used to excellent effect. 

The next phase of the synthesis was installation of the dimethylamino-oxazoline ring system. This was constructed from the oxazolidinone precursor 19. Oxazolidinone formation occurred when 25 was reacted with thionyl chloride. The more nucleophilic carbonyl of 19 was then O-alkylated with the Meerwein reagent to give an iminium ion that readily participated in a nucleophilic addition/elimination reaction with dime-thylamine to give 26. The final step of the synthesis was O-deacetylation of 26 with sodium methoxide to provide (—)-allosamizoline hydrochloride in 98% yield after acidification. 

Mechanistic analysis of some key steps in the Simpkins (—)-allosamizoline synthesis... 

Desymmetrization by means of this methodology was successfully applied to a synthesis of key intermediates for mosin B, aspicilin, ga/a-quercitol, and allosamizoline. ... 

Radical additions to 0-alkyl aldoximes, easily accessible from reducing sugars, have been exploited for the synthesis of allosamizoline, the aglycon of aUosamidin [334]. The C ring of anguidine has also been prepared by reductive carbocyclization of an aldehyde on an unsaturated ester [335]. 

Next, Danishefsky s allosamizoline synthesis will be described [143,144]. The key point of their synthetic strategy is the utilization of enzymatic optical resolution to the racemic substrate. As illustrated in O Fig. 8, there are two approaches for the enzymatic optical resolution. One is the enzymatic hydrolysis of a diester [145,146,147], and the other is the enzymatic transacylation of the meso-dk> [148,149,150] (O Fig. 8). In Danishefsky s group, the former route was chosen as the key step. Treatment of diacetate 186 with electric eel acetylcholinesterase provided the monoacetate 187, which was reported by Deardorrf et al. [147]. This work was also applied to the synthesis of PG p2a in Danishefsky s laboratory [151]. On the basis of the success of their synthesis of PG p2a, diacetate 188, which was derived from the 2-alkene-l,4-diol derivative 176, was treated with electric eel acetylcholinesterase as well. Interestingly, this treatment provided the unexpected monoacetate 189 in 95% yield, > 95% ee (O Fig. 8). 

Many syntheses of allosamizoline and its analogues from noncarbohydrate have been reported. "" Carbohydrates have been also used for the synthesis of allosamizoline, which upon suitable protection to be a glycosyl acceptor that can be coupled with the required oligosaccharide donor would led to the total synthesis of allosamidin. 

Synthesis from o-glucose The synthesis of allosamizoline has been achieved by starting with methyl a-D-glucopyranoside (9) (Scheme Selective tosylation of... 

S.3.3.2 Synthesis from o-glucosamine Allosamizoline (8) has also been synthesized from D-glucosamine (Scheme 3). Methyl 2-amino-4,6-0-benzylidene-3-0-benzyl-2-deoxy-a-D-glucopyranoside" (26), obtained from D-glucosamine hydrochloride (25), was converted into the corresponding M,A -dimethylurea derivative, which underwent hydrolysis with aqueous acetic acid to give the diol 27 (91%). Selective iodination of the primary position and subsequent protection of the secondary hydroxyl group with... 

Another synthesis of (-)-allosamizoline (8) was also carried out using the glucoseamine derivative 44 by an intramolecular cycloaddition of a nitrile oxide to an olefin as a key step (Scheme 5). ° lodination of 44 followed by reductive 3-elimination using zinc in THF afforded the 5-enofuranose 46, whose reaction with ethanethiol in cone. HCl followed by silylation with TBSOTf afforded 47. Dethioacetalization of 47 with HgCl2-CaC03 followed by treatment of the resulting aldehyde with NH2OH afforded the oxime 50, which underwent intramolecular cycloaddition to produce the isoxazoline 51. Alternatively, treatment... 

The carbocyclic analogue of the trehalase inhibitor, trehazolin, has been prepared and reported to have potency indistinguishable from the natural product." The synthesis of other antibiotic-related cyclopentane derivatives such as analogues of mannostatin A, allosamidin (and allosamizolin) and a 4-membered carbocyclic thiazole analogue of oxetanocin, are covered in Chapter 19. 

A synthesis of the insecticidal compound allosamidine (plus isomer) and aglycone allosamizoline has been reported. The key step in the formation of the allosamizoline involved the oxyamination of cyclopentene 71 with osmium tetroxide and sodio ethyl A -chlorocarbonate in the presence of mercury(U) trifluoroacetate to afford 72 together with regioisomers. See also Chapter 19 for other syntheses of allosamizoline. 

A total synthesis of ( )-allosamizoline from a symmetrical trisubstituted cyclopentene has been reported, and a synthesis of allosamidin and its (1- 3) linked isomer includes a review of the preparation of the starting aminocyclitol and disaccharide moieties. The synthesis of allosamizoline and allosamidin and isomers is also mentioned in Chapters 3 and 18. 

A preliminary report has appeared on the synthesis of allosamizoline, the aglycone of allosamidine (See also Chapter 19, for a full account) as well as the synthesis of the aminooxazoline from the known Helv. Chim. Acta., 1979, 62, 1990) 2R,3S,4R-4-... 

A total synthesis of allosamidin is mentioned in Chapter 3. Full details of the synthesis of allosamizoline, the aglycone of allosamidin, have been reported. Studies of allosamidin biosynthesis using labelled D-glucose and D-glucosamine indicate that the latter sugar is the precursor to each N-acetyl-o-allosamine and to the allosamizoline component. ... 

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