Giuliana Cardillo

Enantioselective synthesis of 2-benzyloxy alcohols and 1,2-diols via alkylation of chiral glycolate imides. A convenient approach to optically active glycerol derivatives

Abstract The alkylation of the chiral enolates of glycolate imides 2a and 2b proceedes in highly diastereoselective manner to give 2-substituted products in good yield. Reductive cleavage with LiBH4 affords the corresponding 2-benzyloxyalcohols 3a-c and 11a-b which are successively converted to 1,2-diols in high optical purity. By this method (R)-1-propanoyloxy-2, 3-propanediol 9 and (S)-1-tridecyloxy-2,3-propanediol 14 , a glyceride extracted from sponges Plocamiidae, have been synthesized, starting from 2a and 2b , respectively.

A new synthesis of both the enantiomers of 4-amino-3-hydroxybutanoic acid (gabob) and mm2 calculations for rotamers of the intermediate oxazolidin-2-on

Abstract The easy Chromatographic separation of the diastereomertic mixture of oxazolidin-2-ones 4a and 4b allows to synthesize pure R-(-)- la and (S)-(+)-GABOB 1b . The 1H NMR pattern of 4a and 4b can be correlated with the configuration at C-5 and this relationship is confirmed by MM2 calculations for rotamera of 5-substituted oxazolidin-2-ones.

A novel, efficient synthesis of (±)-erythro-sphingosine

Abstract A stereoselective synthesis of (±)-erythro-sphingosine triacetate ( 1 ) is described. The key reaction that determines the right stereochemistry is the iodocyclization of 1-trichloroacetimido-(2E,4E)-octadecadiene ( 5 ). The 4,5-dihydro-l, 3-oxaztne ( 6 ) through cleavage with HC1 and treatment with Amberlyst A 26 in the AcO- form, followed by full acetylation, affords ( 1 ) in good yield.

Synthesis of Dehydro-β-amino esters

The allylic amination of acetates and carbonates affords dehydro-beta-aminoesters, which are useful precursors of biologically active compounds. The uncatalyzed reaction proceeds via a S(N)2 mechanism. On the other hand, under palladium-catalyzed conditions, the reaction shows a strong solvent-dependent regiocontrol, affording exclusively one of the two possible regioisomers with complete transfer of chirality from the substrates to the products.

A New Diastereoselective Synthesis of anti‐α‐Alkyl α‐Hydroxy β‐Amino Acids

As part of an ongoing project concerning the synthesis of enantiomerically pure α-hydroxy β-amino acids, we have now developed a general strategy allowing the synthesis of anti-α-alkyl α-hydroxy β-amino acids. Our procedure involves the intermediate formation of trans-oxazolines, which are alkylated at C-5 with good to high diastereoselectivity and then hydrolysed under mildly acidic conditions, affording in quantitative yield the corresponding hydroxy amides. The starting (R)-3-amino-3-phenylpropanoic acid and (S)-3-aminobutanoic acid were obtained in enantiomerically pure form by selective enzymatic hydrolysis of the corresponding phenylacetylamides with penicillin G acylase.

Stereocontrolled reactions through heterocyclic intermediates

- New methods of double bonds halofunctionalization of allylic and homoallylic alcohol and amine derivatives have been developed. Carbonates, imidates, urethanes and amides have been cyclized to heterocyclic intermediates whose hydrolysis leads to diols, triols and aminoalcohols. This method has been applied to the synthesis of deoxyaminosugars (ristosamine and daunosamine), sphinganines, sphingosine and 2-amino-2-deoxytetritols. Moreover the use of chiral auxiliaries allows to obtain easily separable diastereomeric mixtures of heterocyclic intermediates, useful for the synthesis of biologically active compounds such as propranolol and GABOB.

Synthesis of the Phenylserine−Leucine Dipeptide Fragment Present in the Antibiotic Lysobactin from an Aziridine‐2‐imide Precursor

The ring expansion of (2R′,3S′) or (2S′,3R′)-N-(α-amino acyl)-aziridine-2-imides and the mild hydrolysis of the resulting oxazoline-4-imides gives (2R,3S)-phenylserine−leucine or (2S,3R)-phenylserine−leucine dipeptides. In particular, the latter fragment is present in the depsipeptide antibiotic Lysobactin.

Iodocyclofunctionalization of (E)-1-trichloroacetimidoalk-2-enes. Synthesis of (±)-erythro-sphinganine triacetate

From the iodocyclization of (E)-1-trichloroacetimido-octadec-2-ene, 5-iodo-4-pentadecyl-2-trichloromethyl-5,6-dihydro-4H-oxazine was unexpectedly obtained, whose structure was assigned from i.r. and 1H n.m.r. spectra. The stereostructure of this oxazine was further confirmed by chemical evidence: thus, the compound was hydrolysed on silica gel to give 2-iodo-3-trichloroacetamido-octadecan-1-ol, and successive treatment with Amberlyst A 26 (CO32– form) yielded cis-5-hydroxymethyl-4-pentadecyl-4,5-dihydrooxazole, whose configuration was determined by 1H n.m.r. data. Acidic hydrolysis of this oxazole and acetylation led to erythro-3-amino-octadecane-1,2-diol triacetate. To ascertain definitively the structure of this triacetate, 3-trichloroacetamido-octadec-1-ene was cyclized, to yield 5-iodomethyl-4-pentadecyl-4,5-dihydrooxazole as a 45:55 cis : trans mixture. After hydrolysis of the cis-isomer, treatment with Amberlyst A 26 (AcO– form), and full acetylation, the aforementioned erythro-triacetate was obtained.Confirming the unequivocal assignment of the stereostructure of 5-iodo-4-pentadecyl-2-trichloro-methyl-5,6-dihydro-4H-oxazine, its acidic cleavage gave 3-amino-1-iodo-octadecan-2-ol hydrochloride. By treatment of this salt with Amberlyst A 26 (AcO– form), full acetylation of the product afforded (±)-erythro-sphinganine triacetate in good yield, contaminated with a minor amount of the regioisomeric 3-amino-octadecanediol triacetate.

A regio- and stereoselective synthesis of methyl α-L-ristosaminide hydrochloride

Abstract Methyl 4-0-trichloroacetimido-2,3,6-trideoxyhex-2-en-α-L-erythropyranoside 3 , prepared from methyl 2,3,6-trideoxyhex-2-en-α-L-erythropyranoside 2 , underwent a halocyclization reaction to the halooxazoline 4a or 4b , depending on the halonium ion source. By hydrolysis under acidic conditions, 4a and 4b were converted to the corresponding hydrochlorides 5a and 5b , respectively. The dehalogenation reaction, performed with Bu3SnH, gave methyl 3-amino-2,3,6-trideoxy-α-L-ribopyranoside hydrochloride ( methyl α-L-ristosaminide ) 1 in very good yield.

Microwave-assisted ring expansion of N-acetyl 3′-unsubstituted aziridine in the presence of Lewis acids

Abstract The microwave-assisted ring expansion of N-acetyl 3′-unsubstituted aziridine-2-imides and N-acetyl 3′-unsubstituted aziridine-2-esters to oxazolines is reported. The regioselectivities of the rearrangements depend upon the reaction conditions, such as the Lewis acid selected and the solvent.