Untersuchung der Biologie von Naturstoffen: systematische Strukturvariation durch umgelenkte Totalsynthese

A Bioinspired Catalytic Oxygenase Cascade to Generate Complex Oxindoles

“…In a separate reaction of the pure aldehyde (E)-13 a and the ketoester 15 a (R = Et, R 2 = Me), the adduct 14 a was obtained in similar yields and diastereoselectivities. [16] Highly enlightening results from the groups of Karlin [4a,b,e,9d,17] and Ito [18] on Cu-O 2 chemistry, along with support from crystallographic [19] and spectroscopic [20] evidence, strongly suggest an electrophilic reactivity of a side-on-type peroxo intermediate for aromatic o-hydroxylation of monophenols by tyrosinase. [21] The oxygenase transformation of the oxindole 12 into 13 seems to follow a similar reaction mechanism.…”

Total Synthesis and Biological Evaluation of (−)‐Englerin A and B: Synthesis of Analogues with Improved Activity Profile

“…This material fuelled an extensive SAR study [8] aimed to clarify the role of englerins two ester side chains (green boxes). Diverting the synthesis [9] at an earlier intermediate allowed us to probe the influence of the isopropyl group (red box). When devising a strategy for a total synthesis program, it is mandatory to plan for the preparation of both enantiomers when the absolute configuration is unknown.…”

Translating Nature’s Library: The Bryostatins and Function‐Oriented Synthesis

“…However, the functional role of the remaining A-ring structure (carbons C6 through C8) was unknown, other than its contribution to conformational rigidity and/or lipophilicity. We therefore targeted des -A-ring spacer domains of type 60 – 63 [3a,66,67] to explore this hypothesis. By eliminating the C6–C8 linkage, up to two stereocenters could be deleted, thereby facilitating access to these fragments.…”

“…However, such synthetic advances require time while the need to supply many agents is often immediate. [2] Function-oriented synthesis (FOS) [3] offers a strategy to address this problem. [4] FOS draws on the realization that the value of natural as well as non-natural compounds is driven not only by their structures and the synthetic challenges presented therein but also and significantly by their function (e.g., biological activity or use as a therapeutic, material, nanodevice, probe, imaging agent, diagnostic, ligand, conductor, sensor, catalyst, or molecule of theoretical interest).…”