Amino polyols

Related to the nitrile oxide cycloadditions presented in Scheme 6.206 are 1,3-dipolar cycloaddition reactions of nitrones with alkenes leading to isoxazolidines. The group of Comes-Franchini has described cycloadditions of (Z)-a-phenyl-N-methylnitrone with allylic fluorides leading to enantiopure fluorine-containing isoxazolidines, and ultimately to amino polyols (Scheme 6.207) [374]. The reactions were carried out under solvent-free conditions in the presence of 5 mol% of either scandium(III) or indium(III) triflate. In the racemic series, an optimized 74% yield of an exo/endo mixture of cycloadducts was obtained within 15 min at 100 °C. In the case of the enantiopure allyl fluoride, a similar product distribution was achieved after 25 min at 100 °C. Reduction of the isoxazolidine cycloadducts with lithium aluminum hydride provided fluorinated enantiopure polyols of pharmaceutical interest possessing four stereocenters. 

Substituted 4,5-dihydro-5-vinylisoxazoles (40), obtained by regio- and stereospecific cycloaddition of nitrile oxides to dienes, undergo smooth osmium-catalyzed c/s-hydro-xylation to give amino-polyol precursors (equation 28)45. The reaction is anti selective, the diastereomeric ratios ranging from 73 27 up to 99 1. Highest stereoselectivities were observed when R3 was methyl. Thus, whereas osmylation of 40a afforded a 78 22 mixture of 41a and 42a, respectively, in 80% overall yield, similar treatment of 40b resulted in a 92 8 mixture of 41b and 42b, respectively, in 70% overall yield. The cycloaddition-osmylation sequence allows control of the relative configuration of up to 4 contiguous asymmetric centers. 

Amino Polyols, Amino Sugars, and Amino Acids. 425... 

Since the stereochemical outcome of LiAfflLj reduction of isoxazolines is predictable according to the parameters described above (140,293), this concept was exploited in efficient syntheses of various amino polyols and sugars as represented... 

Less well-established cycloaddition chemistry has also found application in the synthesis of heterocyclic compounds in recent years. An example is the intramolecular cycloaddition of silyl nitronates that has been employed by Ishikawa and Saito to afford 136 in their synthesis of amino polyols (Scheme 14) <2003OL3875>. 

Catalytic transfer hydrogenolysis of a BOM ether and benzyloxycarbonyl (Cbz) group using formic acid as the hydrogen source launched the finale to a synthesis of the Tbnicamycin antibiotics [Scheme 4.274].71 Subsequent treatment of the crude amino pentaol 274 2 with 13% formic acid in methanol at 40 °C for 5 h then resulted in methanolysis of the jV-Boc and isopropylidene acetal groups. To complete the sequence, the TBS ether group was deleted with HF to furnish the amino polyol 274.4 in 90% overall yield for the 3-step sequence. 

Amino-polyols, such as 1-aminodeoxy-D-sorbitol or D-(-l-)-glucosamine, as well as adenine, underwent selenenylation-acylation at the amino groups by dichloride 102 and thus their 2-benzisoselenazol-3(2//)-onyl derivatives 108 and 109 were obtained <2003SC1301> (Scheme 40). The organoselenium-modified /3-CDs 110 and 111 were synthesized in a similar way <2002HCA9>. 

The amino groups (-NH2) generated by the reaction with alkylene oxides (PO, EO) hydroxyalkyl groups, transforming the initial amine into an amino polyol (reaction 13.2). 

The resulting amino polyols (structure 13.2) do not have a polyetheric structure, but if the addition of alkylene oxide continues by extension of the chains derived from hydroxyl groups, real structures of polyether polyols are formed (reaction 13.3). 

Of course the hydroxyl number presented in Table 13.2 is a hypothetical one (the amines do not have hydroxyl groups), but it is very useful for the calculation of the final amino polyol hydroxyl number, after alkoxylation. 

Obviously, the extension of the polyetheric chain using KOH as catalyst needs a purification step. The advantage of using tertiary amines or the catalytic effect of the amino polyol is very important from the technological point of view because the purification step is eliminated, the production cycle is short and the yield in polyether polyol is very high. 

By increasing the degree of propoxylation (chain extension), by reacting the resulting amino polyol (14.7), with PO in the presence of a catalyst (for example KOH), until the hydroxyl number becomes 390-410 mg KOH/g, the resulting viscosity decreases, but remains very high, around 140,000-145,000 mPa-s, at 25 °C, which makes it difficult to use in practice [3, 4, 13]. 

An interesting approach to chiral 2-amino-1,3-diols makes use of an asymmetric Staudinger reaction that incorporates the required functional groups into a jS-lactam nucleus. The condensation of imine 818 with benzyloxyketene produces jS-lactam 819 with 95% diastereo-selectivity [218]. After dearylation with cerric ammonium nitrate the amino polyol is released as an isoserine derivative (821) by cleavage of the jS-lactam with chlorotrimethylsilane in methanol [227] (Scheme 110). The amino group can be removed by conversion to isocyanide 823 followed by reduction with tris(trimethylsilyl)silane in the presence of AIBN, which furnishes erythro a,j8-dialkoxy ester 824 without racemization. 

The principle of exciton coupling between vicinal benzoate chromophores has been extended to other aromatic carboxylic acid derivatives , including those of ring-substituted benzoic acids, 9-anthranoic acid (141) and p-methoxycinnamic acid (142). These derivatives have been widely used for the determination of the absolute stereochemistry in polyol natural products. The circular dichroism of the A -p-bromobenzoyl group combined with various 0-, 0,0 -di- and 0,0, 0"-tii-(p-bromobenzoyl) derivatives of 2-amino-2-deoxygalactopyranoside and an iV-anthranoyl group combined with tri-, tetra- and penta-p-methoxycinnamoyl derivatives of acyclic 1-amino polyols were studied to improve and develop microscale CD methods for the structural study of amino sugars. 

The synthesis of sphingosines, ceramides and other amino polyols has seen a number of reports this year. A synthesis of sphingofungin D 217, the anifungal metabolite of Aspergillus... 

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