A conceptually novel construction of the 6a-hydroxypterocarpan skeleton - Synthesis of (±)-variabilin.

A new access to the 6a-hydroxypterocarpan variabilin was established. Key step of this concise total synthesis is a challenging cyclization of a haloketone via halogen-metal exchange and subsequent intramolecular addition to the carbonyl function.

Straightforward Synthesis of DFO* - An Octadentate Chelator for Zirconium-89.

DFO* is an octadentate chelator able to form highly stable chelates with Zirconium-89 (89 Zr) for nuclear medicinal applications in Positron Emission Tomography (PET).[1,2] The synthesis of DFO* and its scale-up remains challenging by reported synthetic protocols. For this reason, we set out to develop a de novo synthesis of a hydroxamate-containing building block suitable for the coupling to the commercially available DFO (desferrioxamine B, mesylate salt) yielding, after deprotection, the desired chelator DFO* in a more efficient procedure. Highlights of the new synthesis of DFO* reported herein are less synthetic steps and the isolation of the desired product DFO* by using solid phase extraction (SPE), thus avoiding tedious HPLC purification. DFO* is obtained in excellent purity (92-98 %) and an overall yield of approximately 29 %. In addition, the isolated trifluoroacetic acid (TFA)-salt of DFO* displays an improved solubility in organic solvents (DMSO, DMF, methanol), which will facilitate its use for the preparation of structurally diverse derivatives suitable for bioconjugation chemistry and the development of 89 Zr-labeled radiotracers.

Asymmetric one-pot transformation of isoflavones to pterocarpans and its application in phytoalexin synthesis.

Phytoalexins have attracted much attention due to their health-promoting effects and their vital role in plant health during the last years. Especially the 6a-hydroxypterocarpans glyceollin I and glyceollin II, which may be isolated from stressed soy plants, possess a broad spectrum of bioactivities such as anticancer activity and beneficial contributions against western diseases by anti-oxidative and anti-cholesterolemic effects. Aiming for a catalytic asymmetric access to these natural products, we establish the asymmetric syntheses of the natural isoflavonoids (-)-variabilin, (-)-homopterocarpin, (-)-medicarpin, (-)-3,9-dihydroxypterocarpan, and (-)-vestitol by means of an asymmetric transfer hydrogenation (ATH) reaction. We successfully adapt this pathway to the first catalytic asymmetric total synthesis of (-)-glyceollin I and (-)-glyceollin II. This eight-step synthesis features an efficient one-pot transformation of a 2'-hydroxyl-substituted isoflavone to a virtually enantiopure pterocarpan by means of an ATH and a regioselective benzylic oxidation under aerobic conditions to afford the susceptible 6a-hydroxypterocarpan skeleton.