Total synthesis of a protected form of sphingofungin E using the [3,3]-sigmatropic rearrangement of an allylic thiocyanate as the key reaction.
An approach to the stereocontrolled synthesis of the protected form of sphingofungin E (32) starting from the known protected d-glucose derivative 3 is described herein. For the construction of a tetrasubstituted carbon atom that is substituted with nitrogen, the [3,3]-sigmatropic rearrangement of thiocyanate 8 was employed. Subsequent functional group interconversions afforded the highly functionalized fragment, allylic bromide 26. Its coupling reaction with the known C(12) hydrophobic segment 2, followed by further manipulation, completed the total synthesis.
Study of Stereoselectivity in Organometallic Additions to 1,2-O-Isopropylidene-O-R-α-D-xylopentodialdo-1,4-furanose
Tibor Gracza* and Peter SzolcsanyiDepartment of Organic Chemistry, Faculty of Chemical Technology, Slovak University ofTechnology, Sk-812 37 Bratislava, Slovakia. Tel. (0421) 7 59325 167, Fax (0421) 7 529 68 560,http://www.chtf.stuba.sk/KATEDRY/koch/new_gracza.htm* Author to whom correspondence should be addressed. ?-mail gracza@chtf.stuba.sk.Received: 2 August 2000 / Accepted: 8 December 2000 / Published: 21 December 2000Abstract: Diastereofacial selectivity of the addition of organometallic reagents to 1,2-O-isopropylidene-O-R-α-D-xylopentodialdo-1,4-furanoses (6) was studied.Keywords: Organometallic reagents, stereoselectivity, addition to carbonyl.IntroductionGoniofufurone (+)-1 and 7-epi-goniofufurone (+)-2 were recently isolated from the stem bark ofThai Goniothalamus giganteus Hook f., Thomas (Annonaceae) and shown to exhibit cytotoxicactivity in tests with several human tumor cell lines [1,2]. We have developed a total synthesis of bothdiastereomers (+)-1 and (+)-2 starting from D-glucose [3]. The key steps are the phenyl magnesiumbromide addition to 1,2-O-isopropylidene-α-D-xylopentodialdo-1,4-furanose and palladium(II)-catalyzed oxycarbonylation of the corresponding 1-phenyl-5-hexene-1,2,3,4-tetrols. Whilst the Pd(II)-catalyzed formal O-cyclization and carbon monoxide addition yielded the required bicyclic skeletonswith high regio-preference and excellent threo-selectivity (concerning the newly formed stereocentreat C-3) [4,5], Grignard addition of phenyl magnesium bromide to 6a in tetrahydrofuran led to twodiastereomeric alcohols 7a and 8a in a 1:3 ratio favouring formation of the L-ido diastereomer 8a,possessing the correct stereochemistry for less cytotoxic 7-epi-goniofufurone (+)-2 (Scheme 1).
REARRANGEMENT OF ALLYLIC N-PHENYLFORMIMIDATES TO N-ALLYL-N-PHENYLFORMAMIDES CATALYZED BY PALLADIUM COMPLEXES
The palladium complexes such as Pd(PPh3)4 and Pd(PhCN)2Cl2 catalyzed the rearrangement of allylic N-phenylformimidates to give N-allyl-N-phenylformamides under a mild condition. The reaction courses are strongly influenced by the oxidation state of palladium complexes used.