Stereocontrolled access to optically-enriched oxabispidines

A conceptual framework for analysing and planning synthetic approaches to diverse lead-like scaffolds

“…An ambiphile pairing reaction (4 + 5) leading to the formation of a cyclic sultam (6) is shown in Panel B: 23 here, both of the building blocks are bi-connective, and so the overall 50 approach is classified as a bi/bi process. The formation of the bridged bicyclic scaffold 11 is even more powerful because three building blocks are used, and three bonds are formed to two of these building blocks; 25 the approach exploits two tri-connective (7 and 8) and one bi-connective (9) building block, and thus 55 receives the tri/tri/bi classification. The classification of synthetic approaches thus depends on the building blocks that are exploited (compare Panels A and B).…”

“… 32) (Panel A). The approach could be extended to yield related scaffolds through cyclisation of alcohol ( 33) or 25 N-sulfonyl amide ( 34 or 35) nucleophiles (Panel B). In addition, a related Cu-catalysed cyclisation reaction of alkynyl amines has been exploited in the synthesis of related scaffolds (e.g.…”

“…For example, the "build-couple-pair" 20,** framework is broad, and has been used to describe synthetic approaches in which building blocks are combined to yield alternative molecular scaffolds. Ambiphile pairing reactions 23 (in which pairs of bifunctional 25 building blocks are combined to yield scaffolds) may be considered to be a subset of reactions that exemplify the "buildcouple-pair" approach.…”

“…For 25 example, three bi-connective building blocks -the aldehyde 87, the enol ether 88, and the methoxycarbonyl-substituted nitro compound 89 -were exploited in the synthesis of the phosphodiesterase (PDE) IVb inhibitor 90 (Scheme 13). 41 Initially, the aldehyde 87 and the nitro compound 89 were Examples of scaffolds that may be prepared using a related two-component process exploiting cyclic imines.…”

“…3 The field of biology-oriented synthesis (BIOS), 4 for example, seeks to focus on biologically-relevant chemical space by using biologically-validated scaffolds 5,6,7 to inspire library design. 25 Figure Scaffold diversity of the organic chemistry universe. 8 The 24 282 284 cyclic compounds in the CAS registry in 2008 are grouped from the most popular 5% to the least popular 5% of scaffolds.…”