A series of novel naphthoquinone fused cyclic α-aminophosphonates, 2-alkoxy-3, 4-dihydro-2H-naphtho[2,3-e][1,4,2] oxazaphosphinane-5, 10-dione 2-oxide 3–17 and naphthoquinone fused cyclic α-aminophosphonic monoester 18 were synthesized for the first time. These cyclic α-aminophosphonates were evaluated for antitumor activity on four human tumor cell lines, and three of them showed significant cytotoxicity (IC50: 0.019–5.15 μM) comparable to that of the reference drug doxorubicin. Furthermore, inhibition assays for topoisomerase II-mediated relaxation of supercoiled DNA indicated that the naphthoquinone fused cyclic aminophosphonates were catalytic inhibitors of topoisomerase II.

A convenient and rapid method was developed for the synthesis of various N-phosphoramino α-aminoalkylphosphonates through Mannich type reactions under catalyst- and solvent-free conditions with excellent yields.

The synthesis of a novel quinone fused phosphorus heterocycle, 2-chloro-3, 3-disub- stituents-3, 4-dihydro-2H-naphtho[2, 3-e][1, 4, 2]-oxazaphosphinane-5, 10-dione 2-oxide (3a–g), was described for the first time. These compounds, which have a readily leaving group Cl, can serve as intermediates of many quinone fused phosphorus heterocycles. The structures of 3a–g were characterized by using common spectroscopic methods. According to the X-ray structure of 3a, these compounds may be used as DNΑ-intercalators.

Functionalised bicyclic exo-glycals are readily obtained by base-catalysed (typically MeONa in MeOH) alkynol cycloisomerisation of ethynylated cyclic saccharides. Thus, base treatment of the phenylethynyl- and halogenoethynylated 1-O-acetyl-ribofuranoses 22 - 24 and the 4-ethynylated 1-thioglucopyranosides 30 - 33 gave - after deacetylation - selectively the (Z)-configured exocyclic enol ethers 26 - 28 (84 - 91%) and 34 - 37 (63-76%), respectively, resulting from a trans-5-exo-dig cyclisation. The ring closure to the trans-dioxahex-ahydroindans 34 - 37 is favoured by a concerted intramolecular protonation of the intermediate vinyl anion by the neighbouring HO-C(3). Cycloisomerisation of the 6-O-acetyl-4-(phenylethynyl)-1-thio-α-D-glucopyrano-side 39 occurred via the corresponding phenylethynylated allenes to provide the galacto-configured (Z)- and (E)-cis-dioxahexahydroindans 40 (30%) and 41 (51%). Surprisingly, the HO-C(4) unprotected α-D-galactopyranosyl-butα-1,3-diyne 15 and the β-D-glucopyranosyl-butα-1,3-diyne 51 (and its 2-bromoethynyl analogue) undergo a 6-exo-dig ring closure to the 2,5-dioxabicyclo[2.2.2] octanes 16 - 19 and 52/53, respectively, the ring closure requiring a boat conformation (B1,4 for 15, 1,4B for 51). Ring strain (anti-reflex effect) prevents an alkynol cycloisomerisation of 4-(phenylbuta-1,3-diynyl, bromoethynyl, or iodoethynyl) levoglucosan 56 - 59, and 56 reacted by elimination to the hex-1-ene-3,5-diyne 59 (82%), while isomerisation of 57 and 58 led to epimeric mixtures of the haloallenes 60 (82%) and 61 (68%).

An improved method for the synthesis of Diphenyl α-(diethoxythiophosphorylamino) methylphosphonates under mild conditions is described. It consists of the reaction of diethyl thiophosphoramidate (1) with triphenyl phosphite (3) and a substituted benzylaldehyde or ketone (2) by a one-pot procedure with the aid of acetyl chloride.