Completely stereocontrolled aldol reaction of chiral ß-amino acids.

A general protocol to independently access stereoisomerically pure ß'-hydroxy-ß-amino acid derivatives that is based on dibutylboron triflate-mediated aldol reaction of suitably protected ß-amino acids bearing chiral oxazolidinone auxiliary is reported. The method smoothly afforded syn-aldol (α,ß'-syn) products in pure form and excellent isolated yield. Both α,ß-syn and α,ß-anti isomers are readily accessible solely through the choice of the oxazolidinone chirality. This method allows for the preparation of stereoisomeric ß'-hydroxy-ß-amino acid derivatives that were previously unreported.

Total synthesis of manzamine A and related alkaloids.

Total syntheses of three structurally complex marine natural products, manzamine A, ircinol A, and ircinal A, are reported. The route pivoted on the construction of a late-stage protecting-group-free pentacyclic enol triflate coupling partner, from which all three family members were accessed divergently via palladium-catalyzed reactions. The rapid synthesis of this key pentacyclic enol triflate was achieved by a highly convergent union of five fragments through a stereoselective Michael addition, a three-component nitro-Mannich lactamization cascade, an unprecedented and highly stereoselective reductive nitro-Mannich cyclization cascade, a stereoselective organometallic addition, and a Z-selective alkene ring-closing metathesis. Altogether this chemistry has allowed the shortest synthetic route to date for manzamine A (18-step longest linear sequence) via a late-stage diversification point that is ideal for future manzamine A analogue synthesis.

Total synthesis of branimycin: an evolutionary approach.

The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization.

Synthesis and analytics of 2,2,3,4,4-d5-19-nor-5alpha-androsterone--an internal standard in doping analysis.

A short and efficient synthesis of pentadeuterated 2,2,3,4,4-d5-19-nor-5alpha-androsterone 7 starting from 19-norandrost-4-ene-3,17-dione 1 by a d1-L-Selectride mediated stereo- and regioselective reduction of the 3-keto group is presented. The use of compound 7 as internal standard for the detection of anabolic steroids via mass spectrometric techniques such as gas chromatography-mass spectrometry (GC-MS) is discussed.

Crotylation versus propargylation: two routes for the synthesis of the C13-C18 fragment of the antibiotic branimycin.

The C13-C18 fragment 3 of the novel antibiotic branimycin was prepared along two highly stereocontrolled routes. The first one uses a standard Roush crotylation protocol, whereas the second one proceeds via an allenyl silane propargylation with unexpected stereochemical consequences, which are discussed in detail.

A tether controlled exo-selective trans-annular Diels-Alder (TADA) reaction.

[reaction: see text] A fully substrate controlled stereoselective route to construct cis-hexahydronaphthalene 4 is described starting from nonracemic butenolide 6. The key step is an exo-selective transannular Diels-Alder reaction (TADA) of tetraene 5, whose intrinsic constraint allows selective formation of one stereodefined product. Compound 4 is a key intermediate in the synthesis of the novel antibiotic branimycin (1).

Toward the synthesis of the antibiotic branimycin: novel approaches to highly substituted cis-decalin systems.

A variety of highly functionalized cis-decalin systems have been prepared by means of the stereoselective transannular Diels-Alder (TADA) reaction of a (Z,E,Z,Z)-tetraene macrolide, and by means of intramolecular nitrile oxide olefin (INOC) or ring-closing metathesis (RCM) annulations to quinic acid derivatives.

First synthesis of a pentadeuterated 3'-hydroxystanozolol--an internal standard in doping analysis.

The first synthesis of 16,16,20,20,20-pentadeuterio-3'-hydroxystanozolol (8) in 26% yield over nine steps is described using moderately priced starting materials and economic amounts of reagents. Compound 8 can be used as an internal standard in screening procedures for anabolic steroids as well as for the quantification of stanozolol metabolites via mass spectrometric techniques, such as LC-MS or gas chromatography-mass spectrometry (GC-MS).

A facile and high yielding synthesis of 2,2,3,4,4-d5-androsterone-beta-D-glucuronide--an internal standard in dope.

A facile six-step synthesis of 2,2,3,4,4-d5-androsterone-beta-D-glucuronide (1) starting from epiandrosterone (2) in 63% yield is described and compared with several alternative synthetic pathways. Compound 1 can be used as an internal standard in screening procedures for anabolic steroids to monitor the hydrolysis step of the steroid glucuronides prior to gas chromatography-mass spectrometry (GC-MS) analysis. Thus, a time consuming solid-phase extraction step to remove possible hydrolysis inhibitors can be omitted.