Total Synthesis. Stick Serine

Oxapenams is a new class of β—lactam antibiotics with broad bioactivities. Clavulanic acid, the first natural oxapenam discovered in 1975, is a powerful β-actamase—inhibitor. It has a carboxy at C—2 and R—configuration at C—5. The second group of oxapenams isolated in 1979 has different radicals such as hydyoxymethyl, carboxy, formyloxymethyl and hydroxyethyl at C-3 but has not carboxy at C-2. They have S-configuration at C-5 and show antifugal activity.From 1983 three series of oxapenams with an amino—acid side chain at C-3 had been discovered, (a) Clavalaine (Ro22-5417) with the alaine side chain at C-3 of oxapenam ring exhibits antibacterial and antifungal activities, (b) Antibiotics G-0069 A, C and clavamycins A, B, C, D, E, F are clavaserine derivatives with antifungal activity. In specially, G-0069 A shows antitumor activity, (c) Antibiotic Tü-1718z is a clavaisothreonine derivative with antibacterial, antifugal and weaker antitumor activities. We decided first to carry out the synthesis of clavaserine in order to complete the total syntesis of this series of antibiotics and to study the the structure-activity ralationship further.As an oxapenam derivative clavaserine could be obtained by first forming β-lactam ring and then forming oxazolidine ring. According to retrosynthetic analysis clavaserine could be separated into two parts: β-lactam part—4—acetoxy—2—azetidinone and side—chain alcohol.There are three chiral centers in side梒hain alcohol. Because the configuration at C-3 in clavaserine is R, the configuration at C-4 in side-chain alcohol...