Role of Macrocyclic Conformational Steering in a Kinetic Route toward Bielschowskysin

Macrocyclic furanobutenolide-derived cembranoids (FBCs) are the biosynthetic precursors to a wide variety of highly congested and oxygenated polycyclic (nor)diterpenes (e.g. plumarellide, verrillin or bielschowskysin). These architecturally complex metabolites are thought to originate from site-selective oxidation of the macrocycles’ backbone and a series of intricate transannular reactions. Yet the development of a common biomimetic route has been hampered by a lack of synthetic methods for the pivotal furan dearomatization in a regio- and stereoselective manner. To address these shortcomings, a concise strategy of chemo- and stereoselective epoxidation followed by a kinetically-controlled furan dearomatization is reported. The surprising switch of facial a:b-discrimination observed in the epoxidations of the most strained E-acerosolide versus E-deoxypukalide and E-bipinnatin J derived macrocycles has been rationalized by the 3D-conformational preferences of the macrocyclic scaffolds. The downstream functionalization of FBC-macrocycles was also studied, and how the C-7 epoxide configuration was retentively translated to the C-3 stereogenicity in dearomatized products under kinetic control to secure the requisite (3S,7S,8S)-configurations for the bielschowskysin synthesis. Unlike previously speculated, our results suggest that the most strained FBC-macrocycles bearing a E-(D7,8)-alkene moiety may stand as the true biosynthetic precursors to bielschowskysin and several other polycyclic natural products of this class

Synthesis of Briarane Diterpenoids: Biomimetic Transannular Oxa-6π electrocyclization Induced by a UVA/UVC Photoswitch

A biomimetic synthesis of briareolate ester B (<b>3</b>) from briareolate ester L (<b>1</b>) via the intermediate briareolate ester G (<b>2</b>) has been achieved through a unique transannular oxa-6π electrocyclization induced by UVA light. UVC irradiation of <b>3</b> triggered a rapid retro-6π electrocyclization to establish an unprecedented photochromic switch. In the ground state, reaction of <b>1</b> led to the formation of a polycyclic γ-spiroketal γ-lactone <b>5</b>, architecturally related to the ether-bridged cembranoids of the cladiellin class

An Iridoid Glucoside and the Related Aglycones from <i>Cornus florida</i>

A new iridoid glucoside, cornusoside A (<b>1</b>), and four new natural product iridoid aglycones, cornolactones A–D (<b>2</b>–<b>5</b>), together with 10 known compounds were isolated from the leaves of <i>Cornus florida</i>. The structures of compounds <b>1</b>–<b>5</b> were established by interpretation of their spectroscopic data. Cornolactone B (<b>3</b>) is the first natural <i>cis</i>-fused tricyclic dilactone iridoid containing both a five- and a six-membered lactone ring. A biosynthesis pathway is proposed for cornolactones C (<b>4</b>) and D (<b>5</b>), the C-6 epimers of compounds <b>1</b>–<b>3</b>

Briareolate Esters from the Gorgonian &lt;em&gt;Briareum asbestinum&lt;/em&gt;

Two new briarane diterpenoids briareolate esters J (&lt;strong&gt;1&lt;/strong&gt;) and K (&lt;strong&gt;2&lt;/strong&gt;) were isolated from the methanolic extract of the octocoral &lt;em&gt;Briareum&lt;/em&gt;&lt;em&gt; asbestinum &lt;/em&gt;collected off the coast of Boca Raton, Florida. The structures of briaranes &lt;strong&gt;1&lt;/strong&gt; and &lt;strong&gt;2&lt;/strong&gt; were elucidated by interpretation of spectroscopic data. Briareolate ester K (&lt;strong&gt;2&lt;/strong&gt;) showed weak growth inhibition activity against human embryonic stem cells (BG02)

Bicyclic C₂₁ Terpenoids from the Marine Sponge <i>Clathria compressa</i>

Three new bicyclic C₂₁ terpenoids, clathric acid (<b>1</b>) and two <i>N</i>-acyl taurine derivatives, clathrimides A (<b>2</b>) and B (<b>3</b>), were isolated from the marine sponge <i>Clathria compressa</i>. The structures of these compounds were elucidated by interpretation of spectroscopic data. Clathric acid showed mild antibacterial activity against several Gram-positive bacteria