Solvent tuning and partition coefficient measurements have identified suitable reagent and solvent combinations for the purification of fluorous Mitsunobu reaction products. The crude reaction mixtures are partitioned between 2/1 HFE-7100/FC-72 and DMF/10 % water to provide reagent (fluorous) and product (organic) fractions.

An unusual reaction between 1,3-dithiane anions and by 5-(alkylsulfanyl)-1-phenyltetrazoles has been discovered in which the dithiane anion formally displaces the 1-phenyltetrazole ring from sulfur to provide a sulfanylated dithiane. KeywordsTetrafibricin; Total synthesis; 1,3-Dithianes; 5-(Alkylsulfanyl)-1-phenyltetrazoles; Nucleophilic additions; Sulfanylations; Sulfur chemistryThe natural product tetrafibricin 1 was isolated in 1993 by Kamayama and coworkers, and they assigned its two-dimensional constitution by a battery of spectroscopic methods 1 . The compound has a linear carbon backbone featuring 11 stereocenters (10 with hydroxy groups and one with a methyl group), is a tetraene, with three isolated trans double bonds, and assorted other functional groups. In 2003, Kishi and coworkers assigned the threedimensional structure (configuration) of 1 without resorting to derivatization or degradation by comparing NMR spectra of the natural product in both chiral and achiral solvents to an NMR database of fragment spectra 2 . Roush 3 and Cossy 4 have described syntheses of fragments of 1.We have advanced a retrosynthetic strategy in Fig. 1 of the disassembled tetrafibricin 1 into six main fragments 2-7. Though the synthesis has not yet been completed, all of the fragments have been made, and assorted couplings have been established 5 . Along the way to making the C21-C30 fragment 4, we encountered an unusual reaction between a dithiane anion 6 and a 5-(alkylsulfanyl)-1-phenyltetrazoles. Herein we describe this reaction, which, in the context of the tetrafibricin synthesis, proved to be a temporary roadblock. We also describe a straightforward detour around this roadblock to complete the synthesis of a modified C21-C30 fragment. RESULTS AND DISCUSSIONThe two fragments 13 and 17 needed to make 4 were synthesized as shown in Scheme 1. Oxidation 7 of commercially available dioxolane alcohol (S)-8 to aldehyde 9 was followed by the Wittig reaction and non-selective epoxidation of the resulting alkene 10 to give a

Two two-compound mixtures of candidate structures for the Phytophthora α1 mating hormone have been synthesized. The mixtures were designed to have differing configurations at C3, but proved to be identical. This suggests that epimerization occurred at C3, and comparison with the data for the natural samples suggest that this is also a mixture of isomers.Phytophthora, derived from Greek "the plant destroyer", is a parasitic genus of organism whose members live in the soil and attack the roots and basal stems of plants. These fungi-like parasites do considerable damage to assorted hosts. 1 For example, Phytophthora infestans was responsible for the blight that precipitated the Irish potato famine in the mid-19 th century. Other Phytophthora induce rot in plants as diverse as strawberries, tomatoes, tobacco, azaleas, coconut trees, and oak trees, among others. The control of these organisms remains difficult.Phytophthora are classified as homothallic and heterothallic depending on whether they reproduce asexually or sexually. The sexual reproduction of heterothallic phytophthora is regulated by hormone secretion, 2 and in 2005 Ojika and coworkers isolated about 1 mg of hormone α1 from the A1 mating type of Phytophthora nicotianae. 3 Based on spectroscopic analysis of this sample and its bis-4-bromobenzoate derivative 2, Ojika proposed that the twodimensional structure (constitution) of hormone α1 was 1,11,16-trihydroxy-3,7,11,15-tetramethylhexadecan-4-one 1 (Figure 1). With four stereocenters, 1 has sixteen stereoisomers, but no information on the three-dimensional structure (configuration) of 1 is yet available.Assigning the configuration of 1 is an especially important goal because Ojika has proposed that 1 is a universal hormone for all heterothallic species of Phytophthora. Yajima and coworkers recently made a mixture that presumably contains all sixteen stereoisomers of 1, and found that this mixture exhibited about 20% of the oospore-inducing activity of the natural sample. 4 They also commented that it was impossible to discriminate between the diastereomers of 1 and 2 by NMR analysis.We have recently used techniques of fluorous mixture synthesis to make stereoisomer libraries of a number of natural products. 5,6 As a prelude to employing this technique to make a library of α1 hormones, we decided to execute a traditional synthesis of the hormone. The goals of this work were: 1) to put in place a route that could subsequently be used for fluorous mixture synthesis, 2) to prove the constitution of 1, and 3) to provide preliminary information about configuration of 1. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and al...

Fluorous mixture synthesis provided all eight diastereomers of the phytophthora hormone α1 with the R configuration at C11 as individual samples after demixing and detagging. The library of all possible bis-Mosher esters (16) was then made by esterification. Complete sets of 1H, 13C and (for the Mosher esters) 19F NMR spectra were recorded, assigned, and compared with each other and with published spectra. Not all of the spectra are unique, and the 1H NMR spectra of the Mosher esters provided the most information. The previous assignment of the natural sample as “all-R” stereoisomer mixed with its 3S-epimer was confirmed.

Dithiane derivatives R 0490Sulfanylation of 1,3-Dithiane Anions by 5-(Alkylsulfanyl)-1-phenyltetrazoles. -An unusual reaction between 1,3-dithiane anions and S-alkylsulfanyl-1-phenyltetrazoles is discovered in an attempted synthesis of the C21-C30 fragment [cf. precursorIV)] of tetrafibricin. The dithiane anion formally displaces the tetrazole ring to provide sulfanylated 1,3-dithiane derivatives [cf. (III), (VII)]. -(GUDIPATI, V.; BAJPAI, R.; CURRAN*, D. P.; Collect. Czech. Chem. Commun. 74 (2009) 5, 771-783; Dep. Chem., Univ. Pittsburgh, Pittsburgh, PA 15260, USA; Eng.) -R. Staver 46-158