Non-covalent series. The synthesis of this new [4.3.0] series started with the simplest of the analogues, the non-covalent inhibitor. Compound 10b was synthesized in 3 overall steps starting with coupling N-Cbz-L-Ser to readily available 5-amino-1-pentene, followed by a telescoped acidcatalyzed oxidative cyclization (Scheme 1). Through the course of condition optimization, it was determined that performing the ozonolysis in presence of triphenylphosphine significantly increased the isolated yields and diastereoselectivity. In addition, a convenient procedure using resin-supported triphenylphosphine was developed in order to facilitate the purifications. Carbonitrile series. The synthesis of 10a was unfortunately much more complex than that of the non-covalent analogue 10b. Many attempts to obtain stereopure α-amino nitrile were unsuccessful; syntheses were long and yielded racemic mixtures. The synthesis was therefore redesigned, adapting chemistry from the Ellman group to obtain enantiopure sulfinylimine 15, followed by a modified Strecker reaction adapted from Mabic et. al. Boronic ester series. This series was prepared following a similar diastereoselective synthetic strategy, starting with the synthesis of sulfinylimine intermediate 15a ( Scheme 3). The imine reacted under modified Ellman copper-catalyzed hydroboration conditions to afford the desired α-sulfinamidoboronic ester 19 with a good isolated yield and high diastereoselectivity. A subsequent transesterification of the pinacol protecting group with the chiral (+)-pinanediol, followed by the deprotection of the sulfinamide group gave the highly diastereopure α-aminoboronic ester hydrochloride salt 20. Peptide coupling of 20 provided the boropeptides, which were subjected to oxidative cleavage and dehydrative cyclization to obtain the corresponding bicycles as the sole diastereomers, confirmed by 1D nOe experiments (Figure ).