Juan A. Tamayo

Synthesis of pentahydroxylated pyrrolizidines and indolizidines.

1,3-Dipolar cycloaddition reaction of nitrone 7 and chemo-enzymatically obtained alkenediols 12 and 13 has been used in the synthesis of pentahydroxylated pyrrolizidines (8 and 10) and indolizidines (9 and 11). The pyrrolizidinic and indolizidinic skeletons were built after internal n-alkylation of the suitably functionalized pyrroloisoxazolidine intermediates obtained by the necessary protecting group manipulations. This method expands the scope of cycloaddition reactions in the synthesis of new and highly polyhydroxylated sugar-like alkaloids.

CHIRAL BUILDING-BLOCKS BY CHEMOENZYMATIC DESYMMETRIZATION OF 2-ETHYL-1,3-PROPANEDIOL FOR THE PREPARATION OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS

Abstract 2-Ethyl-1,3-propanediol 1 and its related di-O-acetate 2 were desymmetrized by partial chemoenzymatic acetylation and deacetylation, by Pseudomonas fluorescens lipase (Amano P.; PFL), to (R)-1-O-acetyl-2-ethyl-1,3-propanediol 3. On treatment of 3 with I2/Ph3P/imidazole the related (S)-1-O-acetyl-2-ethyl-3-iodopropanol 4 was obtained and transformed into the corresponding triphenylphosphonium salt 5. Reaction of [(S)-3-acetoxy-2-ethylpropylidene]triphenylphosphorane 6, prepared from 5, with 2,3:4,5-di-O-isopropylidene-β- d -arabino-hexos-2-ulopyranose 7 gave (Z)-3-C-acetoxymethyl-1,2,3,4,5-pentadeoxy-6,7:8,9-di-O-isopropylidene-β- d -manno-dec-4-ene-6-ulo-6,10-pyranose 8 which was hydrogenated to 9 and subsequently deacylated to 10. Treatment of 10 with Me2CO/H+ caused a rearrangement to (3R,4R,5S,6R,9R)-9-ethyl-5-hydroxy-3,4-isopropylidenedioxy-1,7-dioxaspiro[5.5]undecane 11, which closely matched the skeleton of the talaromycins.

Polyhydroxylated Pyrrolizidines. Part 7. Stereoselective Synthesis of Unnatural Analogs of (+)‐Casuarine from Partially Protected DGDP

A new synthetic approach to analogs of (+)‐casuarine (2a and 2b), a natural pentahydroxylated pyrrolizidinic alkaloid in a highly stereocontrolled manner, is reported herein. An orthogonally protected polyhydroxylated pyrrolidine, such as (2S,3R,4R,5R)‐3,4‐dibenzyloxy‐2′‐O‐tert‐butyldiphenylsilyl‐2,5‐bis(hydroxymethyl)pyrrolidine [3, protected DGDP (2,5‐dideoxy‐2,5‐imino‐d‐glucitol)], easily available from d‐fructose, was chosen as the source of chirality and functionalization. †For Part 6 of the series, see Ref. 1.

Lipase-mediated partial resolution of 1,2-diol and 2-alkanol derivatives: towards chiral building-blocks for pheromone synthesis

Abstract 1,2-Propanediol 5 , 1-chloro-2-propanol 8 and its related 2- O -acetate 9 were partially resolved by chemoenzymatic acetylation and deacetylation, in the presence of Pseudomonas fluorescens lipase (Amano P.; PFL), to ( R )-(−)-1-acetoxy-2-propanol 6 , ( R )-(+)-2-acetoxy-1-chloropropane 9 and ( R )-(−)-1-chloro-2-propanol 8 , respectively. On the other hand, treatment of (2 RS )- 2 with vinyl acetate in ether and Chirazyme ® L-2 gave 2- O -acetyl-1,3,4-trideoxy-5,6:7,8-di- O -isopropylidene-β- d - manno -non-5-ulo-5,9-pyranose 1 and 1,3,4-trideoxy-5,6:7,8-di- O -isopropylidene-β- d - gluco -non-5-ulo-5,9-pyranose 11 , respectively. Compound 10 was subsequently deacylated to 12 . Both alcohols 11 and 12 were treated with Me 2 CO/H + to cause their rearrangement to (2 S ,5 R ,8 R ,9 R ,10 S )-10-hydroxy-8,9-isopropylidenedioxy-2-methyl-1,6-dioxaspiro[4.5]decane 3 and its (2 R)- epimer 4 , which closely matched the skeleton of the odour bouquet minor components of Paravespula vulgaris (L.).

Response of parasitoids Dendrosoter protuberans and Cheiropachus quadrum to attractants of Phloeotribus scarabaeoides in an olfactometer.

The braconid Dendrosoter protuberans and the pteromalid Cheiropachus quadrum are two parasitoids of the olive bark beetle, Phloeotribus scarabaeoides. Several chemicals such as α-pinene, β-pinene, 2-decanone, 2-nonanone, decanal, undecanal, and n-butyl acetate have been identified as attractants in the laboratory for this scolytid. Under red light at 27°C in a laboratory olfactometer both parasitoids oriented positively to both enantiomers of α-pinene, and females also responded to 2-decanone. Significant responses did not occur under white light or at lower temperatures. These results suggest that α-pinene and 2-decanone could be involved in the location of P. scarabaeoides by its parasitoids. Consequently an attracticidal control tactic for this scolytid that included these chemicals could eliminate part of the parasitoid population. In an integrated pest management program, this problem should be considered.

Hexulose Derivatives and Lipase‐Mediated Diastereomeric Resolution in the Enantiospecific Total Synthesis of (−)‐Talaromycins C and E

Diastereomeric enzymatic (Chirazyme® L-2, c.−f., C2) resolution of 3-C-acetoxymethyl-1,2,3,4,5-pentadeoxy-6,7:8,9-di-O-isopropylidene-β-D-gluco- and -D-manno-dec-6-ulo-6,10-pyranose (6), obtained from “diacetone D-fructose aldehyde” (3) and the corresponding phosphorane from (3-benzyloxy-2-ethylpropyl)triphenylphosphonium iodide (2), has enabled us to synthesize spiroketals (3R,4S,5S,6R,9R)- and (3R,4S,5S,6R,9S)-9-ethyl-3,4-isopropylidenedioxy-1,7-dioxaspiro[5.5]undecane (7 and 8). An attempt to transform 8 into (−)-talaromycins G and 9-epi-A was unsuccessful. However, (−)-talaromycins C and E could be enantiospecifically prepared from spiroketal 7 in twelve steps.

Lipase mediated resolution of 1,3-butanediol derivatives: chiral building blocks for pheromone enantiosynthesis. Part 3†

Abstract ( R,S )-1,3-Butanediol 5 was kinetically resolved by enzymatic acetylation with vinyl acetate under the presence of Chirazyme™ L -2, c–f, yielding ( S )-1- O -acetyl-1,3-hydroxybutane 6 and ( R )-1,3-di- O -acetyl-1,3-butanediol 7 with enantiomeric excesses of 91% ( E =67.3). Compounds 6 and 7 were easily transformed into the corresponding ( S )-3- O -(2-methoxyethoxymethyl)-3-hydroxybutanal 10 and ( R )-3-benzyloxybutanal 19 , through a protection–deprotection and functional group interchange methodology. Subsequent reaction of 10 and 19 with 3-(methoxycarbonylpropionylmethylene)triphenylphosphorane afforded methyl ( E , S )-8- O -(2-methoxyethoxymethyl)-4-oxo-5-nonenoate 12 and ( E , R )-8-benzyloxy-4-oxo-5-nonenoate 20 . The alkenes 19 and 20 were then catalytically hydrogenated to the corresponding saturated esters 13 and 21 . Treatment of 13 and 21 with 1,2-ethanedithiol/F 3 B·OEt 2 afforded dithioketals 14 and 22 , which were respectively reduced to ( S )-1,8-dihydroxy-4-nonanone ethylidenedithioketal 15 and ( R )-8- O -benzyl-1,8-dihydroxy-4-nonanone ethylidenedithioketal 23 . Finally, deprotection of 15 by catalytic hydrogenation under acidic conditions gave the expected (5 S ,7 S )-(−)-7-methyl-1,6-dioxaspiro[4.5]decane 1 . The (5 R ,7 R )-(+)- 1 enantiomer was analogously prepared from 23 . Both compounds were formed by this procedure with an e.e. of 91%.

SYNTHESIS OF BRANCHED-CHAIN HEXULOSE DERIVATIVES AS MODEL FOR THE SYNTHESIS OF TALAROMYCINS

The synthesis of 3,5-dideoxy-1,2-O-isopropylidene-5-C-hydroxymethyl-β-D-erythro- (1) and α-L-threo-hexulopyranose (2) from 3-deoxy-1,2-O-isopropylidene-β-D-erythro-hexulopyranose (5) from D-fructose is described, as well as their respective transformation into 3,5-dideoxy-1,2-O-isopropylidene-5-C-hydroxymethyl-β-D-threo-(3) and -α-L-erythro-hexulopyranose (4) by inversion of configuration at C-4.