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Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 04/06 Podcast
Total synthesis of variecolortides A–C

Total synthesis of variecolortides A–C

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 04/06 vor 14 Jahren

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Part I: Total Synthesis of Variecolortides A–C The variecolortides
are structurally intriguing, fungal natural products that present a
unique merger of three major streams of biosynthesis. They can be
traced back to other known natural products, namely the viocristins
and echinulins, and we wanted to prove if they could somehow come
together to form the variecolortides. Thus, these natural products
were prepared in short sequences and their critical linkage was
subsequently investigated. It was found that an unprecedented
hetero-Diels-Alder reaction effected this linkage and furnished the
central spirocyclic core of the variecolortides. Ultimately, a
highly convergent route to all three variecolortides (A–C) was
developed. The natural products were each efficiently synthesized
as racemates in seven steps or less (longest linear sequence),
largely avoiding protecting group chemistry. Part II: Towards the
Total Synthesis of Naphthomycin K and Divergolides C and D
Ansamycins are an important class of natural products that often
show potent antibacterial and antiviral activities. We have engaged
in the total syntheses of several new aminonaphthoquinone
ansamycins, including naphthomycin K and divergolides C and D. A
unified approach to their naphthoquinone core was targeted and led
to the development of a novel, cyano-substituted Danishefsky-type
diene. The latter was used in the synthesis of cyano-substituted
naphthoquinones, naphthalenes and other highly functionalized small
molecules. Since the cyano-substituted naphthoquinones could not be
further elaborated into the desired natural products, alternatively
substituted bromonaphthalenes were instead synthesized over short
sequences. In addition, several strategies towards the synthesis of
an ansa chain fragment of divergolides C and D were developed. Part
III: Synthesis of Photochromic Open-Channel Blockers Optical
control of transmembrane ion channel function with high temporal
and spatial precision opens the door for a better understanding of
neuronal circuits and pharmacological associated questions. Several
red-shifted derivatives of QAQ (quaternary ammonium-
azobenzene-quaternary ammonium), a powerful doubly charged
photochromic blocker, have been synthesized. They allow for remote
control of Kv and Nav channel conductance with light and offer the
opportunity to reversibly silence neuronal activity.