Asymmetric Total Synthesis of a Beer-Aroma Constituent Based on Enantioconvergent Biocatalytic Hydrolysis of Trisubstituted Epoxides

Abstract

A short asymmetric total synthesis of the plant constituent myrcenediol [(R)-1], and (S)-7,7-dimethyl-6,8-dioxabicyclo[3.2.1]octane (2), which is a volatile constituent of the aroma of beer was accomplished via a chemoenzymatic protocol. The key step consisted of a biocatalytic hydrolysis of trisubstituted epoxides bearing olefinic side chains which proceeded in an enantioconvergent fashion, i.e., a single enantiomeric vic-diol was obtained from the racemate in up to 91% ee and 92% isolated yield.

epoxide hydrolase - enantioconvergent hydrolysis - trisubstituted epoxide - beer-aroma

References and Notes

<A NAME="RZ06401SS-1">1</A> Orru RVA. Faber K. Curr. Opinion Chem. Biol.  1999,  3:  16 

<A NAME="RZ06401SS-2">2</A> Kroutil W. Mischitz M. Faber K. J. Chem. Soc., Perkin Trans. 1  1997,  3629 

<A NAME="RZ06401SS-3">3</A> Steinreiber A. Mayer SF. Saf R. Faber K. Tetrahedron: Asymmetry  2001,  12:  1519 

<A NAME="RZ06401SS-4">4</A> Steinreiber A. Osprian I. Mayer SF. Orru RVA. Faber K. Eur. J. Org. Chem.  2000,  3703 

<A NAME="RZ06401SS-5">5</A> Osprian I. Stampfer W. Faber K. J. Chem. Soc., Perkin Trans. 1  2000,  3779 

<A NAME="RZ06401SS-6">6</A> Bohlmann F. Ahmed M. King RM. Robinson H. Phytochemistry  1983,  22:  1281 

<A NAME="RZ06401SS-7">7</A> Barrero AF. Sanchez JF. Altarejos J. Zafra MJ. Phytochemistry  1992,  31:  1727 

<A NAME="RZ06401SS-8">8</A> Hioki H. Ooi H. Mimura Y. Yoshio S. Kodama M. Synlett  1998,  729 

<A NAME="RZ06401SS-9">9</A> Tressl R. Friese L. Fendesack F. Köppler H. J. Agric. Food Chem.  1978,  26:  1422 

<A NAME="RZ06401SS-10">10</A> Naya Y. Kotake M. Tetrahedron Lett.  1967,  26:  2459 

<A NAME="RZ06401SS-11A">11a</A> Masaki Y. Nagata K. Serizawa Y. Kaji K. Tennen Yuki Kagobutsu Toronkai Koen Yoshishu  1983,  26:  545 

<A NAME="RZ06401SS-11B">11b</A> Chem. Abstr.  1983,  101:  23162x 

<A NAME="RZ06401SS-12">12</A> Ibrahim N. Eggimann T. Dixon EA. Wieser H. Tetrahedron  1990,  46:  1503 

<A NAME="RZ06401SS-13">13</A> Curran DP. Heffner TA. J. Org. Chem.  1990,  55:  4585 

<A NAME="RZ06401SS-14">14</A> Crispino GA. Sharpless KB. Synlett  1993,  47 

<A NAME="RZ06401SS-15">15</A>

Since the biocatalytic hydrolysis of trisubstituted epoxides could proceed in an enantioconvergent fashion (not via kinetic resolution), the general use of E-values for the description of enantioselectivities is inapplicable.

<A NAME="RZ06401SS-16">16</A> Hellström H. Steinreiber A. Mayer SF. Faber K. Biotechnol. Lett.  2001,  23:  169 

<A NAME="RZ06401SS-17">17</A> Yamada S. Oh-hashi N. Achiwa K. Tetrahedron Lett.  1976,  29:  2557 

<A NAME="RZ06401SS-18">18</A> Yamada S. Oh-hashi N. Achiwa K. Tetrahedron Lett.  1976,  29:  2561 

<A NAME="RZ06401SS-19">19</A> Kamber M. Pfander H. Helv. Chim. Acta  1984,  67:  968 

<A NAME="RZ06401SS-20">20</A>

In contrast, mesylation proceeded very slowly.

<A NAME="RZ06401SS-21">21</A> Nielsen BE. Lemmich J. Acta Chem. Scand.  1969,  23:  962 

<A NAME="RZ06401SS-22">22</A> Mischitz M. Kroutil W. Wandel U. Faber K. Tetrahedron: Asymmetry  1995,  6:  1261 

<A NAME="RZ06401SS-23">23</A> Kroutil W. Osprian I. Mischitz M. Faber K. Synthesis  1997,  156 

<A NAME="RZ06401SS-24">24</A> Osprian I. Kroutil W. Mischitz M. Faber K. Tetrahedron: Asymmetry  1997,  8:  65 

<A NAME="RZ06401SS-25">25</A> Krenn W. Osprian I. Kroutil W. Braunegg G. Faber K. Biotechnol. Lett.  1999,  21:  687 

<A NAME="RZ06401SS-26">26</A> Morizawa Y. Kanakura A. Yamamoto H. Bull. Chem. Soc. Jpn.  1984,  57:  1935 

<A NAME="RZ06401SS-27">27</A> Vliet MCA. Arends IWCE. Sheldon RA. Synlett  2001,  248 

<A NAME="RZ06401SS-28">28</A> Fournier-Nguefack C. Lhoste P. Sinou D. Tetrahedron  1997,  53:  4353