Minas P. Georgiadis

Synthesis and biological studies of steroidal cis-platinum(II) complexes

Abstract Several new steroidal cis -platinum(II) complexes ( 4a, 4b, 4c and 4d ) were synthesized by treatment of K 2 PtCl 4 with appropriately substituted steroids. The receptor binding affinities ( RBA ) of the prepared complexes, which may be indicative of their selectivity, were evaluated along with the antitumor testing of one of these steroidal cis -platinum(II) complexes. The latter was found to possess activity comparable to cisplatin, with respect to both activity and therapeutic index.

Synthesis of amino acid derivatives of neamine and 2-deoxystreptamine to be used as mutasynthons

ABSTRACT 6′-N derivatives of neamine with alanine, phenylalanine and lysine were synthesized either using an active esters method in one step under controlled conditions, or using a mixed anhydride method after blocking every functional group of neamine and leaving the 6′-amino group free to react. Similarly N,N′-diamino acid and monoamino acid derivatives of 2-deoxystreptamine were synthesized.

Water soluble cis-platinum(II) complexes

Abstract The cis -platinum(II) complexes of 2-desoxystreptamine, D-glucosamine and 1-amino-2-methyl-2-propanol have been prepared and their synthesis is discussed in detail. The complexes were extremely water soluble, thus they were expected to be less toxic than cis -DDP. Their structure has been studied by elemental analysis, infrared and 1 H NMR spectra.

Total synthesis of 4-(d-alanylamino)-2-amino-2,3,4-trideoxy-dl-threo-pentose (3-deoxy-dl-prumycin)

Abstract 3-Deoxy- dl -prumycin ( 1 ) was synthesized from 2-furanmethanol (2-furfuryl alcohol, 2 ) in eleven steps in 15% total yield. Michael addition of azide anion to 2,3-dideoxy- dl -pent-2-enopyranos-4-ulose ( 3 ) and reduction in situ of the adduct afforded the key intermediates 5 and 6 . Introduction of a second azido group with inversion of configuration at C-4 afforded intermediates 14 and 17 , both of which had a threo configuration in regard to C-2 and C-4. Coupling with d -alanine and total deprotection yielded the title compound 1 .

The use of the Strecker reaction for the synthesis of sympathomimetic amine analogues and their cis-Pt(II) complexes

Abstract New amines, designed to satisfy the necessary structural requirements in order to be sympathomimetic, have been prepared via the Strecker reaction and subsequent hydrogenation of several carbonyl compounds [1,2]. We have also synthesized the cis-Pt(II) complexes of the above sympathomimetic amine analogues and tested their anti-tumor properties. Furthermore, the new amines show anti-bacterial activity, in contrast with their biological analogues and the starting materials which were inactive.

X-ray and NMR studies on the rotational isomerism about the C(5)-C(6) bond of 6-substituted methyl 2,3,4,-tri-O-acetyl-6-X-α-D-glucopyranoside derivatives

The rotamers about the C(5)–C(6) bond of a series of 2,3,4-tri-O-acetyl-6-X-α-D-glucopyranozide derivatives resulting by substitution at C(6) or O(6) have been studies with1H-NMR spectroscopy (400 MHz) and X-ray structure analysis. The methyl 2,3,4-tri-O-acetyl-6-O-triphenylmethyl-α-D-glucopyranoside and the N-(I-O-methyl-2,3,4-tri-O-acetyl-α-D-glucopyranose-6-yl)-pyridinium nitrate crystallize in the P21 space group with α=14.940(1),b=11.232(1),c=9.0773(7), and β=94.480(7) anda=7.670(1),b=15.384(3),c=9.624(1) and β=104.90(1), respectively; the methyl 2,3,4-tri-O-acetyl-6-O-nitro-α-D-glucopyranoside and methyl 2,3,4-tri-O-acetyl-6-O-deoxy-6-iodo-α-D-glucopyrano-side crystallize in the P212121 space group witha=5.630(1),b=14.360(1) andc=22.388(3), anda=5.556(1),b=14.303(6) andc=21.963(6), respectively.

Resolution of 2,3-Dideoxy-DL-2-Enopyranos-4-Uloses Via Chromatographic Separation of their Diastereomeric O-tert-Butyloxycarbonyl-L-Alanyl Esters. A Convenient Synthesis of L- and D-Aculose

ABSTRACT A simple and effective procedure for the resolution of 2,3-dideoxy-DL-2-enopyranos-4-uloses is presented. This procedure is based on column chromatographic separation of their diastereomeric O-(N-tert-butyloxycarbonyl)-L-alanyl esters, followed by mild acidic cleavage of the ester function. L-Aculose, 2,3,6-trideoxy-L-glycero-hex-2-enopyranos-4-ulose, is also prepared in satisfactory yield.

Synthesis of Amino Acid and Peptide Derivatives of Aminoglycosides Targeted Against Resistance of Bacteria

Interest in aminoglycoside antibiotics, in spite of their long familiarity, remains high because of their clinical utility. Unfortunately, the latter is limited by oto- and nephrotoxicities and is related to the binding of these polycationic drugs to negatively charged phospholipids and to the subsequent inhibition of lysosomal phospholipases [1,4]. It is also well known that bacterial resistance is associated with specific chemical transformattions in the molecule This has resulted in the research for novel semisynthetic aminoglycoside derivatives that would not be capable of such enzymic modification. The discovery of the most prominent aminoglycoside antibiotics, natural or semisynthetic, are butirosin, amikacin, fortimycin, sporaricin and minosaminomycin, which contain amino acids linked by an amide bond, has emphasized the favorable effects of aminoacyl substituents on aminoglycosides [5].

Hybrid Antibiotics: Aminoglycoside 3-Quinolone or β-Lactam Amides

A wide variety of derivatives of aminoglycosides have been prepared over many years, in the effort to improve the antibacterial activity and decrease their toxicity [1].