Bicyclo[3.2.0]heptane as a Core Structure for Conformational Locking of 1,3‐Bis‐Pharmacophores, Exemplified by GABA

Abstract

The synthesis and X-ray crystal structures of syn and anti 4-N-Boc-aminobicyclo[3.2.0]heptane-1-carboxylic acids are described. The placement of the N-Boc-amino groups in the two stereoisomers in either pseudo-equatorial or pseudo-axial positions renders the molecules conformationally locked, with N-Boc-protected γ-aminobutyric acid (GABA) embedded within the bicyclic core. Despite the different conformations of the urethane and distinct crystal packing, the bicyclic core units of the two stereoisomers adopt virtually identical structures. They correspond to in silico models of the parent bicyclic core and a systematic array of disubstituted derivatives. The study documents an intrinsic property of the bicyclo[3.2.0]heptane core to favor adoption of a boat-like conformation, which is largely unaffected by various substitution patterns. The structural concepts are useful in the design of molecules with spatial and directional fixation of pharmacophoric groups.

Origins of Catalyst-Controlled Selectivity in Ag-Catalyzed Regiodivergent C–H Amination

“…In particular, in TS5 - β , the N–H bond in the six-membered ring is not coplanar with the Ag nitrene, furnishing a nonideal angle for the nitrene C–H abstraction. In addition, the envelope conformation in TS5 - β leads to greater repulsion with the Ag center because of the concave shape of the bicyclic structure . The strain of the concave bicyclic system in TS5 - β causes partial dissociation of the sulfonyl coordination to Ag ( d (O···Ag) = 2.28 Å, whereas d (O···Ag) is 2.18 Å in TS5-γ ).…”

“…In addition, the envelope conformation in TS5-β leads to greater repulsion with the Ag center because of the concave shape of the bicyclic structure. 27 The strain of the concave bicyclic system in TS5-β causes partial dissociation of the sulfonyl coordination to Ag (d…”

Stereoselective and Regioselective Pinacol‐Type Rearrangement of a Fused Bicyclic Oxetanol Scaffold

“…Bicyclic product 3 has a 6‐oxabicyclo[3.2.0]heptane core, which has previously been targeted by different synthetic approaches . In addition to being an analogue of the valued bicyclo[3.2.0]heptane skeleton, it might be expected to undergo interesting rearrangements that arise from the presence of both the protected tertiary alcohol and the strained oxetane ring. However, with the exception of a few analogues of more complex natural products, examples of 6‐oxabicyclo[3.2.0]heptanes with an oxygen function at the 1‐position are virtually unknown , …”

π‐Lewis‐Base‐Catalyzed Asymmetric Vinylogous Umpolung Reactions of Cyclopentadienones and Tropone

“…Chemie Forschungsartikel 26969 a[2+ +2] manner under the catalysis of Pd 2 (dba) 3 and L13,and the bicyclo[3.2.0]heptane architectures 16,w itnessed in numerous natural products [27] or used as valuable building blocks, [28] were constructed in moderate yields with outstanding stereoselectivity.Even the dearomative [2+ +2] annulation of 1a and 2-nitrobenzofuran 17 could be realized to afford the enantiopure tetracycle 18. [29] Moreover,a lkene 19 underwent similar [2+ +2] annulation to give diastereomers 20 a and 20 b, [30] and aF riedel-Crafts reaction was further conducted with the latter one to give the bridged framework 21 with excellent stereoselectivity.…”