Issue in Honor of Prof. M. Makosza ARKIVOC 2004 (iii) 112-119
Having in hand highly stereoselective method for the preparation of syn-7 and anti-7 acetylenic adduct derivatives of N-Boc-O-Me-L-thyrosinal L-4 we directed our efforts towards the synthesis of unnatural anisomycin ent-1. We pursued our studies exploiting compound syn-7 (Scheme 3).
MeO
MeO
MeO
NHBoc TMS
NHBoc
NHBoc
1.H2/Lindlar THF
Bu4NF
2.Ac2O/Py,DMAP
OH OH OAc syn-7 (3R,4S)-8 (3R,4S)-3
MeO
MeO
OsO4/NMO
HNBoc OH
HNBoc OH
+
acetone/H2O
OH
OH
OAc OAc syn,syn-9 syn,anti-9
HNBoc MeO OMs OH MsCl, Py/NEt3, CH2Cl2 N AcO OHMeO OAc H (2R,3R,4S)-2 ent-1 Scheme 3 syn-Adduct 7 was treated with crystalline Bu4NF·3H2O33 giving desilylated compound
(3R,4S)-8 in 88% yield. Subsequent hydrogenation, in the presence of a Lindlar catalyst,34 yielded the vinyl adduct which was treated with acetic anhydride35 affording (3R,4S)-3. This compound could be obtained by the direct addition of a vinyl organometallic reagent to N,Odiprotected- L-thyrosinal L-4 but there is no highly effective procedure for this transformation. syn-Dihydroxylation of (3R,4S)-3 with NMO and OsO436 gave a mixture of diastereoisomeric polyhydroxylated amines 9. The diastereoisomeric ratio was 4:1 in favour of the desired isomer syn,syn-9. After the chromatographic separation the primary hydroxy group of syn,syn-9 was mesylated37 in order to facilitate five-membered ring formation but unfortunately all attempts to do so failed to afford the desired antibiotic ent-1. Similar transformation was successfully accomplished using the Appel procedure by Jäger et al.38 In his case, a polyhydroxylated amine with the neighbouring N-Bn and O-Bn triol, was used as pyrrolidine precursor. In this situation we did not further investigate our approach to the synthesis of anisomycin 1.
In summary, we have presented highly diastereoselective addition of lithium trimethylsilylacetylen (6) to N-Boc-O-Me-L-thyrosinal (L-4), affording anti- or syn-adduct 7 depending on the conditions used. The synthetic interest of these transformations was illustrated by the preparation of the anisomycin precursor (2R,3R,4S)-2.
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