Synthesis of polyazamacrocyclic compounds via modified Richman-Atkins cyclization of beta-trimethylsilylethanesulfonamides.

The Richman-Atkins cyclization remains one of the most widely used methods for the preparation of macrocyclic polyamines. The use of beta-trimethylsilylethanesulfonamides (SES-sulfonamides) for the preparation of polyazamacrocyclic compounds is described. This expands existing Richman-Atkins sulfonamide macrocyclization methodology, and it successfully enables preparation of labile polyaza[n](1,4)naphthalenophanes and polyaza[n](9,10)anthracenophanes, not previously available in appreciable quantities.

High dose methotrexate as a preoperative adjuvant in the treatment of epidermoid carcinoma of the head and neck. A feasibility study and clinical trial.

Thirty patients with operable epidermoid carcinoma of the head and neck were treated with intravenous high dose methotrexate and leucovorin rescue prior to resection. Their clinical courses were compared with those of thirty randomly selected patients matched for tumors site and clinical stage who were treated by surgery alone. No medical or surgical complications associated with methotrexate were encountered. An objective decrease in tumor size (primary lesion or nodal metastases) was noted prior to resection in twenty-three patients (77 per cent). The number of recurrences in the two groups was similar. However, these was a significantly greater disease-free interval in the methotrexate-treated patients (p less than 0.05). No significant differences in survival have been noted to date between the two groups. In view of the absence of complications, the regressions in tumor size, and the increase in postoperative disease-free interval in this trial, evaluation as preoperative adjuvants of higher doses of methotrexate and of other chemotherapeutic agents in combination with methotrexate appears warranted.