Azetidinone antibiotics. 17. A rearrangement of penicillin sulfoxides to 3-methylenecephams via sulfinyl intermediates

Aspects of the chemistry of 6-diazopenicillanate S-oxide and S,S-dioxide

“…129-130 "C (from chloroform-cyclohexane) (Found: M', 388.9656. C12Hl,35C13N0,S requires M , (3 H,t,J 7 Hz,CH,CH,),3.73 (4 H,m,CH3CH, + SCH,), 4.72 (1 H,d,J 2 Hz,4.78 and 4.89 (each 1 H,d,J 12 Hz,HCHCCI,),4.89 (1 H,d,J 2 Hz,5.31 (1 H,s,and 5.49 and 5.77 (each 1 H,d,J 1.4 Hz,vinylic H); G,(CDCl,) 15.14 388.9656); V,,,,(CHCl,) 1 760 and 1 040 cm-'; G,(CDCl,) 1.28 (9,CH,CH,),50.30 (t,56.03 (d,66.88 (t,CH,CH,),67.85 (d,74.57 (t,CHZCCl,),84.30 (d,94.23 (s,CCl,),122.05 and 127.01 (s,t,vinylic C),and 166.32 and 166.39 (each S,carbonyl C); m/z 389 ( M ' ) . 2,2,.-Acetic anhydride (112 mg, 1.1 mmol) was added to a solution of 6aethylthiopenicillanate S-oxide (17) (86 mg, 0.22 mmol) in dimethylformamide (1 ml), and the mixture heated under reflux for 1 h. The mixture was then concentrated under reduced pressure, the residue dissolved in benzene, and the benzene solution washed with water and dried (MgSO,).…”

2.beta.-Hydroxymethyl penicillin

“…5: NMR (CDCl,) 6 p-Nitrobenzyl 2~-(Chloroacetoxymethyl)-6-(phenoxyacetarnido)penicillin la-Oxide (13). A mixture of 0.651 g (1.0 equiv) of the disulfide 4, 0.340 g of AgOAc (2.08 equiv), and 4.1 g of C1CH2CO2H (43.5 equiv) in 15 mL of CHzClz was allowed to stir a t room temperature for 4 h. The reaction mixture was filtered and the filtrate was washed with aqueous NaHC0, and brine, dried (NaS04), and chromatographed on silica gel using a toluene-ethyl acetate gradient to give 0.037 g of 6,0.20 g of 5, and 0.17 g of 7.…”

“…After 30 min the solution was washed with NaHC03, HzO, and brine, dried, (Na2S0,) and chromatographed on silica gel using toluene-ethyl acetate gradient to give 63% I@-oxide 10: NMR (CDCl,) 6 1.22 (s, 3, a-Me), 4.15 (s, 2, CH,Cl), J = 13 Hz, 2, CH2OC(O)CH2Cl), 4.09 (s, 2, CHZCl), 4.56 ( s , 2, PhOCH2) 4.82 (s, 1, H3), 5.28 (s, 2, PNB), 5.60 (d, J = 4 Hz, 1, 4.40, 4.83 (AB, J = 14 Hz, 2, CH20C(O)CH2Cl), 4.55 (s, 2, PhOCHJ, 4.83 (s, 1, HJ, 5.13 (d, J = 4 Hz, 1, Hb), 5.35 (s, 2, PNB),6.20 (4, J = 4, 10 Hz, 1, He); IR (CHC13) 1795 cm-' (P-lactam). p-Nitrobenzyl 2~-(Chloroacetoxymethyl)-6-(phenoxy-acetamid0)penicillin I@-Oxide (IO).…”

Actinomycetes: A Never-Ending Source of Bioactive Compounds—An Overview on Antibiotics Production

“…In the same contest, Kukolja discovered the oxidative ring expansion of sulfoxide 34 yielding 3-methylenecepham sulfoxides ( 39 ) [ 134 ]. The reaction is based on the transformation of sulfoxide ( 34 ) into sulfinyl halide ( 38 ), by means of halogenating agents.…”