Ye Guan, Zhengxiang Zhu, Miao‐kun Sun
2001
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Journal
Main Group Metal Chemistry
Abstract
3 -(Hydrogermyl)propanoic acid and N-(3-(hydrogermyl)propanoyl)amino acids were transformed to the corresponding 5or 8membered germalactones under reduced pressure through intramolecular dehydrocyclization in the absence of catalyst in good yields. A series of 5and 8membered germalactones were synthesized. Biological tests showed that four of these cyclic compounds possess moderate antitumor activity. INTRODUCTION Germa-y-lactones were p rev ious ly syn thes ized by the m o n o b r o m i n a t i o n of 3(trialkylgermyl)propanoic acids followed by hydrolysis of the resulting 3-(dialkybromogermyl)propanoic acids. ' ' ' The discovery of antitumor activity of structurally related germane compounds' prompted us to develop efficient synthesis of germa-y-lactone derivatives carrying various functional groups. In our early work on the synthesis of biologically active trialkylgermylpropanoic acids,' we found that 3(hydrogermyl)propanoic acid and N-(3-(hydrogermyl)propanoyl)-amino acids could be transformed to the corresponding 5and 8membered germalactones in presence of Raney-Ni catalyst.' We report here a more eff ic ient procedure to carry out this t ransformation, namely, the instant cycl izat ion of 3(hydrogermyl)propanoic acids and N-(3-(hydrolgermyl)propanoyl)-amino acids under reduced pressure without use of any catalyst. A variety of 5and 8membered germa-lactones were thus synthesized and their antitumor activity investigated. RESULTS AND DISCUSSION Hydrogermyl propanoic acids la-f were prepared through the reduction of the corresponding bromides with NaBH4 following a procedure we reported previously. Key characteristics of these compounds were summarized in Table 1. These compounds are sufficiently stable at room temperature under atmosphere pressure. Under reduced pressure and at a temperature of 40~50°C, intramolecular dehydrocyclization occurred to afford the corresponding germalactones 2a-f (Scheme 1). No solvent or catalyst was required. It was also found that the bromogermylpropanoic acids could be transformed to the germa-lactones through a one-pot procedure without purifying the intermediate 3-(hydrogermyl)propanoic acid (2e and 2f, Scheme 1, Table 1). \ ' C H C H R Η R=H,CH3.Ph R2Ge(H)CHR'CHRC02H Vacuum 40-50'C *