Jacques Streith

Chiral 5-Methyl-trihydroxypyrrolidines—Preparation from 1,2-Oxazines and Glycosidase Inhibitory Properties

Abstract Chemical transformations of chiral 1,2-oxazines 4, 5 gave the 2,5,6-trideoxy-2,5-imino d -alditols 12b, 13b in the d -altritol and d -talitol series, respectively. Basic aldehyde epimerisation led to the d -allitol isomer 15b. Compound 12b is a potent α- l -fucosidase and α- d -galactosidase inhibitor.

Asymmetric synthesis of potent glycosidase and very potent α-mannosidase inhibitors: 4-amino-4-deoxy-l-erythrose and 4-amino-4,5-dideoxy-l-ribose

Abstract Pyrrolidine amino-sugars, cyclic iminoalditols as well as linear aminoalditols in 4-amino- l -erythrose and 4-amino-5-deoxy- l -ribose series were synthesised by asymmetric hetero-Diels–Alder reaction followed by chemical transformations. 4-Amino-4-deoxy- l -erythrose and 4-amino-4,5-dideoxy- l -ribose were potent β- d -glucosidase, α- d -mannosidase, α- and β- d -galactosidase inhibitors. We have shown that the ribose derivative was a very potent inhibitor of α- d -mannosidase.

Single and double asymmetric induction in Diels-Alder cycloadditions with chiral acylnitroso dienophiles

Abstract Diels-Alder reaction of the achiral 1-silyloxybutadiene 1a with the chiral acyinitroso dienophile 2a gave cycloadduct 4 in high diastereomeric excess (d.e. > 98 %), a result which is undoubtedly due to the C-2 symmetrical chiral dimethylpyrrolidine inductor. Excellent d.e. was also observed when the (R)-prolinol dienophile 2d was reacted with the chiral diene 1b (d.e. = 96 %), whereas cycloaddition of the (S) enantiomer 2e with 1b gave only poor asymmetric induction (d.e. = 4 %). These two latter examples nicely illustrate the influence of “matched pair” (1b/2d) versus “mismatched pair” (1b/2e) upon double asymmetric induction. All herein reported Diels-Alder cycloadditions were regiospecific.

Asymmetric Diels-Alder cycloadditions with acylnitroso dienophiles obtained from L-proline

Abstract N-acylnitroso derivatives of L-proline were formed in situ from the corresponding hydroxamic acids. They reacted easily with 1,3-cyclohexadiene to give the corresponding diastereoisomeric pairs of Diels-Alder cycloadducts with d.e. values ranging from 52 to 68 %.

6-Deoxy-allo-nojirimycin in the racemic and d-series, 6-deoxy-d,l-talo-nojirimycin, their 1-deoxyderivatives and 6-deoxy-2-d,l-allosamine via hetero-Diels-Alder cycloadditions

Abstract Diels-Alder cycloaddition of hexadienal dimethylacetal 3 to achiral acylnitroso-dienophile 5a gave the racemic cycloadducts 7a-c and, to chiral chloronitroso-dienophile 6, enantiomerically pure D-10a as sole adduct. Simple chemical transformations led to 6-deoxy-2- d,l -allosamine 15b, to 6-deoxy- d,l and d -allo-nojirimycin 15a, D-15a, to 6-deoxy- d,l -talo-nojirimycin 15c as well as to their 1-deoxy-derivatives 16a, D-16a, 16c via their crystalline 1-deoxy-1-sulfonic acid derivatives (sulfite adducts). Amino-sugars 16a,c are mixtures of α- and β-anomers and of the corresponding imines.

PYRAZOLINO-DIAZEPINES AND HOMODIAZEPINES

1,2-Diazepines 1 undergo various (2π + 4π) as well as (4π + 2π) cycloadditions and lead to bridged adducts 9 and to pyrazolino-diazepines 13 respectively. The elusive 1,7-diazanorcaradiene tautomers 2 could not be trapped through cycloaddition reactions. 1-Pyrazoline 11 as well 2-pyrazo]ine 13a loose a nitrogen molecule by thermal activation and lead to the expected homodiazepines 16 and 17.

Stereospecific double glycolisation of 1,2-dihydropyridines with OsO4. Synthesis of (±) aminoarabinose- and of (±) aminoaltrose derivatives [1].

Abstract Double glycolisation of 1,2-dihydropyridines 1 led stereospecifically and in good yield to the corresponding (±) aminoarabinose- and (±) aminoaltrose derivatives 5 . Hydrogenolysis of the N-benzyloxy carbonyl piperidinose 5b gave directly the 1-desoxy derivative 7a .

CHIRAL N-DIENYL-L-PYROGLUTAMIC ESTERS IN ASYMMETRIC HETERO-DIELS-ALDER REACTIONS WITH ACYLNITROSO DIENOPHILES

Abstract Asymmetric Diels-Alder reaction of the N-dienyl-L-pyroglutamic esters 1a-h with acyl nitroso dienophiles 4a-h gave diastereoisomeric adducts 6a-n, 7a-n with 12–90 % de, depending on solvents and temperature. An interpretation was gived. The “allylic effect” ( π C=C − σ ∗ N-C MO interactions) was found to be effective to account for the conformations of the adducts.

Cycloaddition reactions of 1,2-diazepines with nitrile oxides. synthesis of 1,2,9-triaza-8-oxabicyclo-[5.3.0]-3,5,9-decatriene derivatives

Abstract A new heterocyclic system, 1,2,9-triaza-8-oxabicyclo-[5.3.0]-3,5,9-decatriene 4 , has been synthesized by regiospecific 1,3-dipolar cycloaddition of nitrile oxides to the imine double bond of 1,2-diazepines. Bis-adduct 5a is obtained in only trace amounts showing that the imine double bond is more reactive than the Δ 4 -olefinic bond.

De Novo asymmetric synthesis of two 5-amino-5,6-dideoxy-D-allose derivatives

Abstract Diels-Alder cycloaddition of sorbic aldehyde derivative 9 and of sorbic acid 10 with the chiral chloro-nitroso dienophile 7 led with excellent regio- and diastereoselectivity to the chiral cycloadducts 11a and 12 , respectively. Catalytic osmylation of their Bzl-derivatives 11b and 13b , followed by reductive cleavage of the NO bonds, gave ultimately the chiral aminoallose derivatives D-5 and D-6 which are potential glycosidase inhibitors.