Cyclit‐Reaktionen, IV ¹⁾ Synthese von enantiomerenreinen Conduriten und Amino‐Conduriten

Abstract

Die S:hlusselzwischenstufe fur alle hier beschriebenen Synthesen ist das 1-0-Tosylat 7 des Quebrachits (l), aus dem uber 8 die 1 L-Form des Condurits B ( 5 ) und uber 13 die 1 L-Form des Condurits F (17) Cyclitol Reactions, IV *) Synthesis of Enantiomeric Conduritols and Amino-ConduritolsThe key-intermediate for all syntheses described in this paper is the 1-0-tosylate 7 of quebrachitol (1). This leads, via 8, to the 11-conduritol B (5) and, oia 13, to the 1 L-conduritol F (17). Selective displacement of the equatorial tosyloxy group in compound 13 by azide gave 16. From this the epoxide 24 and the corresponding olefin 26 were synthesized. Treatment of 26 with triphenylphosphane gave the optically active amino-conduritol31. The azido olefins 25 and 26 convert at high temperatures by [3,3]sigmatropic rearrangement to their enantiomers 28 and 29 respectively. These rearrangements lead to racemates.Condurite und Amino-Condurite sind interessante potentielle Inhibitoren fur Glycosidasen *). Alle isomeren Condurite und eine Reihe von Amino-Conduriten wurden bisher synthetisiert 'I. Bei allen Synthesen wurden jedoch Racemate erhalten. Unseres Wissens sind bisher keine enantiomeren Verbindungen dargestellt worden. Wir berichten jetzt uber die Synthese optisch aktiver Condurite, wobei als chiraler ,,precursor" der Quebrachit eingesetzt wird, der bei der Rohgummiproduktion abfallt.Quebrachit ist der 2-0-Methyl-~-chiro-inosit (1). Im Verlauf der Synthese ist sornit eine prekare 0-Methylether-Spaltung erforderlich. AuOerdem muB bei allen Umwandlungen der Verbindung die Chiralitat des Molekuls erhalten bleiben. Durch Umsetzung mit Dimethoxypropan erhalt m a n aus 1 die Diisopropylidenverbindung 2, die sich anschlieBend in das Tosylat 3 uberfuhren IaBt. 3 erwies sich als geeignetes Derivat fur die 0-Methylether-Spaltung. Die Reaktion gelingt mit Bortribromid in Methylen~hlorid~), wobei die 0-Tosylgruppe nicht mit abgespalten wird. Die entscheidende selektive Blockierung an der 1-OH-Gruppe bleibt somit erhalten und man gelangt unter gleichzeitiger Abspaltung der Isopropylidengruppen zum Monotosylat 7.

Synthesis of (−)‐Conduritol C (1L‐Cyclohex‐5‐ene‐1,2,3/4‐tetrol)

“…In 1958, Angyul et al [14] presented a synthesis of (+)-condurito1 E ( = 1~-cyc~ohex-5-ene-l,2/3,4-tetro~; (+)-5). In 1981, Paulsen et al [15] reported the syntheses of (-)-conduritol B ( = 1~-cyclohex-5-ene-l,3/2,4-tetrol; (-)-2) and (-)-conduritol F ( = 1~-cyclohex-5-ene-l,2,4/3-tetrol; (-)-6)4).…”

Total Syntheses of (−)‐Conduritol B ((−)‐1L‐Cyclohex‐5‐ene‐1,3/2,4‐tetrol) and of (+)‐Conduritol F((+)‐1D‐Cyclohex‐5‐ene‐1,2,4/3‐tetrol). Determination of the Absolute Configuration of (+)‐Leucanthemito

“…The same approach has been applied now to the stereoselective total syntheses of (-)-conduritol B ((-)-3) which was prepared for the first time by Paulsen et al [13] and of (+)-conduritol F ((+)-1) whose characteristics were found to be identical with those of natural (+)-leucanthemitol.…”

“…(15 ml), dried (MgSO,), and evaporated. The residue was purified by column chromatography on silica gel (Lobar, Et20/petroleum ether 1:9) yielding 2.5 g of a colourless oil containing 2.1 g (70%) of (-)- 13 [a]::6 = -17.5, [a]:& = -28.3 (c = 2.9, CHCI,). IR (film): 3260,2950(film): 3260, ,2930(film): 3260, ,2900(film): 3260, ,2860(film): 3260, ,1470(film): 3260, ,12S0,1170(film): 3260, ,1120(film): 3260, ,1080 of (-)-lZ (776 mg, 1.6 mmol) and 40% aq.…”

Desymmetrization of a Silyl-2,5-cyclohexadiene. Synthesis of (+)-Conduritol E and (−)-2-Deoxy-allo-inositol

“…Their ability to inhibit oligosaccharide-processing enzymes provides a wide range of possible applications in chemotherapy for these compounds, since glycoproteins are involved in numerous biochemical processes . This has stimulated enormous synthetic efforts recently, and several asymmetric approaches to these substrates have been proposed, among the most efficient of which is the microbial oxidation of aromatic precursors . We propose here a general strategy directed toward the synthesis of polyhydroxylated cyclohexanes through desymmetrization of silyl-2,5-cyclohexadienes using Sharpless asymmetric dihydroxylation .…”

“…In summary, we have demonstrated that the desymmetrization of a readily available silyl-2,5-cyclohexadiene using asymmetric dihydroxylation affords an efficient and rapid entry into cyclohexane skeletons having four or five stereogenic centers in a stereocontrolled manner. This strategy is competitive in terms of cost, efficiency, and versatility with other approaches to similar substrates. ,, The chlorosilane precursor 4a is inexpensive, and both enantiomers are theoretically accessible. Further manipulation of intermediates such as 6 or 7 should also provide the means to access other cyclitols and related analogues.…”