Nucleophilic additions to N-glycosylnitrones part IV Asymmetric synthesis of N-hydroxy-α-aminophosphonic and α-aminophosphonic acids

The addition of phosphite anions and of tris(trimethylsilyl) phosphite (P(OSiMe₃)₃) to N-glycosyl-C-arylnitrones was examined. While these nitrones proved inert towards the phosphite anions, they reacted with P(OSiMe₃)₃ under catalysis by Lewis acids. Thus, P(OSiMe₃)₃ reacted with the crystalline (Z)-N-glycosylnitrones 2 and 8 to give the optically active N-hydroxy-α-aminophosphonic acids 4 and 10 , respectively, and hence the α-aminophosphonic acids 5 and 11 in yields up to 92% and with an enantiomeric excess (e.e.) up to 97% (Scheme 1). The absolute configuration of the phosphonates depend upon the nature and – in one case – upon the quantity of the catalyst (Figure). Upon catalysis by HCIO₄ or Zn(OTF)₂, p(OSiMe₃)₃ added to 2 to give, in both cases, the (+)-(R)-phenylphosphaglycine 5 (optical purity 79–84 and 90–93%, resp.). The optical purity (o.p.) was hardly influenced by the amount of these catalysts (0.02-;1 equiv.). However, catalysis by ZnCl₂ gave, with trace quantities of the catalyst, (–)-(S)- 5 (o.p. 79%), while an equimolar amount of ZnCl₂ yielded (+)-(R)- 5 (o.p. 82%). The HClO₄-catalyzed addition of P(OSiMe₃)₃ to the nitrone 14 (Scheme 2) led to (+)-(R)-N-hydroxyphosphavaline 15 (78%) and hence to (–)-(R)-phosphavaline 16 (71% from 14 e.e. 95%). Under conditions leading from the nitrones 2 , 8 , 14 , and 20 (Schemes 1 and 2) predominantly to (R)-α-aminophosphonic acids, the addition of P(OSiMe₃)₃ to nitrone 18 , possessing a benzyloxy substituent as an additional potential ligand for the catalyst, gave (S)-phosphaserine 19 . The addition of P(OSiMe₃)₃ to the nitrone 20 , catalyzed by Zn(OTf)₂, led to (+)-(R)-N-hydroxyphosphamehionine 21 (71%, e.e. 77%) and hence to (–)-(R)-phosphamethionine 22 (77% from 20 , e.e. 79%). Catalysis by trace quantities of ZnCl₂ gave (+)-(S)- 22 (85%, e.e. 61%). The enantiomerically pure aminophosphonic acids 5 , 11 , and 16 were obtained by recrystalliztion. The e.e. of the N-hydroxyaminosphosphonic acids 10 , 15 , and 21 and the aminophosphonic acids 5 , 11 , 16 , and 22 were determined by the HPLC analysis of the dimethyl N-naphthoyl-α-aminophosphonats 7 , 13 , 17 , and 23 , on a chiral stationary phase.     

An improved synthesis of morpholino-glycoamino acids

The current synthesis of hybrid morpholino-glycoamino acids through double reductive amination is characterized by modest yields and lengthy reaction times. We propose an optimized procedure that results in improved yields and the shortest reaction times reported so far.     

An improved synthesis of Fmoc-N-methyl-alpha-amino acids

A highly efficient and environmentally more benign synthesis of Fmoc-N-methyl-alpha-amino acids from the corresponding Fmoc-amino acid, via intermediate 5-oxazolidinones, has been developed by using Lewis acid catalysis for the reductive opening of the oxazolidinone ring.     

An improved synthesis of homopteroic and homofolic acids

A more practical synthesis of homopteroic and homofolic acids involving condensation of 2,4,5-triamino-6(1H)pyrimidinone ( 3 ) with 1-acetoxy-4-[N-acetyl-(p-carbethoxyphenyl)amino]-2-butanone ( 7 ) is described. The biological activities of homofolic ( 1-b ) and homopteroic ( 2-b ) acids were compared and found to be identical with the activities of these products prepared by the unambiguous route.     

An improved synthesis of 1-phenylpentafluoropropenes

1-Phenylpentafluoropropene and a number of its para- and ortho-substituted derivatives were prepared in high yields by reaction of hexafluoropropene with etheral solutions of corresponding phenylmagnesium bromides in sealed glass tubes under autogenous pressure. The products were obtained as mixtures of the Z and E isomers, which ratios varied from 1/2 to 1/6 in favour of the E forms. ¹⁹F n.m.r. and i.r. spectra and b.p. of the 1-phenylpentafluoropropenes are reported.     

Optically active α-aminophosphonic acids from ureidophosphonates

The preparation of both levorotatory and dextrorotatory α-aminobenzylphosphonic acid by the hydrolysis of substituted ureidophosphonates is described. This method represents an alternative to phosphite addition to unsaturated C-N compounds.     

An improved synthesis of 1-methyl-2,5-piperazinedione

A new synthesis of 1-methyl-2,5-piperazinedione in three steps starting from sarcosine is described. This method proceeds in higher overall yield (49%) than previous methods.     

An improved method of synthesis of N-protected L-amino acids as their benzoxymethyl esters

An improved method for the synthesis of L-amino acids as their benzoxymethyl esters has been reported. All the synthesized compounds were characterized by (1)H NMR, EI-MS and IR spectroscopic methods.     

An improved synthesis and refined crystal structure of 1-methyluracil

A modification of a previously reported synthesis of 1-methyluracil which simplifies the isolation of the compound is reported together with a refined X-ray analysis of the title compound.     

An improved synthesis of resveratrol

In this article we report an improved total synthesis of resveratrol, increasing the overall yield from 22 to 71%. The synthesis reported in our previous publication was made up of two fundamental steps: a Wittig reaction and a Heck coupling. Here we studied these steps separately to increase the individual yields. The yield of the Wittig reaction was increased up to 98%; however, we could not find better reaction conditions for the Heck coupling than those reported in the previous article.     

An improved synthesis of tetramesitylporphyrin

We report a simple two-step one-flask procedure for the synthesis of tetramesitylporphyrin in 29% yield. Pyrrole and mesitaldehyde react at room temperature to form tetramesitylporphyrinogen. The addition of an oxidant yields the porphyrin. Macrocycle formation and oxidative aromatization are thus performed separately. The reaction at higher temperature results in a lower yield of porphyrin.     

An improved synthesis of cyclohexenothioxanthenones

An improved synthesis of cyclohexanothioxanthenones in high yield (70-90%) by treatment of thiosalicylic acid ( 4 ) or 2,2′-dithiosalicylic acid with 1,2,3,4-tetrahydronaphthalene ( 5 ) in the presence of concentrated sulfuric acid or a mixture of 95% sulfuric acid with 27-30% fuming sulfuric acid (in 5:1 to 2:1 v/v ratio) was described. The crude product consisted of three isomers which were isolated and identified. These isomers are 1,2-, 2,3- and 3,4-cyclohexanothioxantenone ( 1, 2 , and 3 ).     

An improved synthesis of diiodonoradamantane

Τhe synthesis of 3,7-diiodo-tricyclo[3.3.1.0^3,7]nonane, the main precursor of noradamantene, by iodination of the corresponding diol via its dimesylate affords a threefold higher yield than the direct iodination of the diol. Neither the dimesylate nor the cyclic sulfate of the diol yields noradamantene upon reduction with sodium amalgam.     

An improved synthesis of norcocaine

An improved, high yielding procedure for the preparation of norcocaine from cocaine is described. The synthesis is accomplished by controlling the pH during the potassium permanganate oxidation. A quantitative conversion of N-benzoylecgonine methyl ester into norcocaine by dry, hydrogen chloride-dioxane is also included.