Elisabeth Öhler

An Intramolecular Case of Sharpless Kinetic Resolution: Total Synthesis of Laulimalide

The microtubule-stabilizing antitumor agent laulimalide (1) has been obtained in by new synthetic route. The carbon skeleton was assembled by means of Julia-Kocienski (C16-C17) and Horner-Wadsworth-Emmons (C21-C22) olefinations. Still-Gennari olefination was used for the C2-C3 ring closure. The key step of the synthesis was a regioselective C16-C17 matched Sharpless asymmetric epoxidation.

Easy access to the epothilone family-synthesis of epothilone B

Abstract An easy access to four out of five naturally occurring epothilones (A-E, 1–5 ) is reported. Key steps are an enantioselective Mukaiyama type aldol reaction, ( E )- and ( Z )-selective olefinations, and a sulfone alkylation.

A novel and versatile synthesis of heterocyclic aldehydes using dialkyl 3-oxo-1-alkenyl-phosphonates.

Abstract Dialkyl 1,2-epoxy-3-oxoalkyl-phosphonates, easily prepared from the corresponding 1-alkenyl-phosphonates, react with ambident nucleophiles to dialkyl 1-hetaryl 1-hetaryl-1-hydroxymethyl-phosphonates, which can be transformed to heterocyclic aldehydes.

Synthesis of the C15–C27 fragment of the antitumor agent laulimalide

Abstract A stereocontrolled synthesis of the C15–C27 fragment of laulimalide is described. Key features are a divergent–convergent synthesis from ( R )-glycidol, an interesting formation of a trisubstituted double bond via ring closing metathesis with Grubbs’ ruthenium catalyst and a site selective protection of a syn -1,2-diol.

Synthese, Reaktionen und NMR-Spektren von 2-Brom-3-oxo-1-alkenyl- und 3-Oxo-1-alkinyl-phosphonsäure-dialkylestern

Dialkyl (E)-3-oxo-1-alkenylphosphonates (1), on reaction with bromine and subsequent HBr-elimination, yield the isomeric β-bromovinyl derivatives (Z)-3 and (E)-3 and the alkinylphosphonates4. β-Bromovinyl compounds3 can also be obtained by reaction of1 withNBS in aqueous solution. The configuration of the β-disubstituted vinylcompounds is assigned from their13C-NMR spectra. Both bromovinyl compounds3 and alkinylderivatives4 are used for regioselective syntheses of acylsubstituted pyrazolylphosphonates5.

Synthesis of the C(11)–C(20) segment of the cytotoxic macrolide epothiline B

Abstract Compound 11, representing the C(11)C(20) segment of the macrolide epothilone B (1b) has been prepared using two Wittig reactions and a Sharpless asymmetric epoxidation as the key steps.

Cyclisierungsreaktionen von Diazoalkenyl-phosphonsäureestern Synthese von Pyrazolyl- und 2,3-Benzodiazepinylphosphonsäureestern

Tosylhydrazones3 and4 of dialkyl 3-oxo-1-alkenylphosphonates1 and 1-oxo-2-alkenylphosphonates2, respectively, react with aqueous sodium carbonate to give the pyrazoles7 in excellent yields. Under analogous conditions the tosylhydrazone9 of diethylo-vinylbenzoyl phosphonate (8) affords diethyl 2-hydroxy-1-indanyl phosphonate (10). Upon thermolysis of the sodium salt12 generated from9 in anhydrousD M E, one obtains, depending on the reaction conditions, either the 1-H-benzodiazepinyl derivative14 or its 5H-isomer15. At room temperature the diazo compound13 cyclizes slowly to give14, which can be isomerized to15 by action of base.

Ein einfacher Weg zu α-substituierten (E)-3-Oxo-1-alkenylphosphonsäureestern

Zusammenfassungα-Substituierte β-Acylvinylphosphonate3 mitE-Konfiguration [R2CO-CH=C(R1)-P(O)(OR′)2], werden in guten Ausbeuten durchWittig-Reaktion von Acylphosphonsäureestern1 [R1CO-P(O)(OR′)2,R1=Alkyl oder Aryl] mit (2-Oxoalkyliden)triphenylphosphoranen2 [R2CO-CH=PPh3,R2=Alkyl, O-Alkyl oder CH2X (X=Br, OMe, CO2Et)] erhalten.Abstractα-Substituted dialkyl (E)-β-acylvinylphosphonates [R2CO-CH=C(R1)-P(O)(OR′)2,3], are easily obtained in good yields byWittig-reaction of dialkyl acylphosphonates1 [R1CO-P(O)(OR′)2,R1=alkyl or aryl) with 2-oxoalkylidene triphenylphosphoranes2 [R2CO-CH=PPh3,R2=alkyl, O-alkyl and CH2X (X=Br, OMe, CO2Et)].

Grubbs' RCM in the Total Synthesis of the Microtubule Stabilizing Drug Laulimalide

Two independent syntheses of the microtubule stabilizing antitumor agent laulimalide are described, which mainly differ with respect to the macrocyclization step. The first synthesis employs a Still–Gennari olefination and the second one an Alexakis-type, allylsilane/acetal addition to close the final ring. For the construction of the dihydropyran subunits, RCM methodology and alternative strategies are presented in comparison.

Synthesis ofD-apio-β-D-furanosyl maleimide, an analogue of showdomycin with transposed hydroxymethyl group

SummaryApioshowdomycin (3-(D-apio-β-D-furanosyl)-1H-pyrrole-2,5-dione,2) has been prepared as an analogue of the C-nucleoside showdomycin (1) in eight steps and with 5% overall yield, starting from 2,3-O-isopropylidene-D-apio-β-D-furanose (3).ZusammenfassungAusgehend von 2,3-O-Isopropyliden-D-apio-β-D-furanose (3) wurde in acht Stufen und 5% Gesamtausbeute Apioshowdomycin (3-(D-Apio-β-D-furanosyl)-1H-pyrrol-2,5-dion,2), ein Analoges des C-Nucleosids Showdomycin (1), hergestellt.