RECENT PROGRESS ON THE CHEMICAL SYNTHESIS OF ANNONACEOUS ACETOGENINS AND THEIR STRUCTURALLY MODIFIED MIMICS - Medicinal Chemistry of Bioactive Natural Products - page 424

CH(OMe) 2

OHC
EtO 2 C

SmI 2 , MeOH

O O

O -5 ° C, 15 min

OBn O

CH(OMe) 2

182 183

MOM

MOMO

O CHO

Co(modp) 2

O

O

O

O 2 , TBHP

OH

OBn

O

C 9 H 19

OMOM

CO 2 Et

184 185

MOMO MOMO

C 10 H 21 O C 10 H 21 O

O O

OH OMOM

OMOM MOMO

MOMO 187

186

1. 188 , Pd(PPh 3 ) 3 Cl 2 ;

TBDPS O

2. H 2 , Rh(PPh 3 ) 3 Cl;
3. 10% HCl in MeOH, DCM

O

I

( ) 2

188

O

mucocin

Scheme 10-31. Total synthesis of mucocin by Takahashi et al. (route two).

derivative) and terminal alkyne 177 (prepared from D-mannitol derived compound)
furnished key compound 178, which was a mixture of epimers at the newly formed
chiral center. It was also found that CeCl 3 could greatly promote the reaction; how-
ever, the desired stereochemistry of new carbinol center was not favorable. After
reduction of triple bond, this hydroxyl group was oxidized and then reduced by
L-seletride, which gives the alcohol in correct configuration. Additional transforma-
tions gave one segment 179 with both THP and THF rings established. The other
segment 180 was prepared from L-xylose and converted into the vinyl iodide 181
via a radical reaction. The coupling conditions and later elaboration are similar to
that described in Scheme 10-28.
More recently, Takahashi et al. developed the second route to mucocin 82
(Scheme 10-31). A SmI 2 -initiated free radical reaction was used to construct the
cis-THP ring, and Co(II)-mediated oxidation furnished the trans-THF ring. The
trans/trans-diene 182 (prepared from (1E,5E,9E)-cyclododecane-triene) was con-
verted into di-aldehyde 183 by Sharpless AD and desymmetry step as well as other
routine steps. Treatment of 183 with SmI 2 in a short time afforded cis-THP com-
pound 184 in high yield, and the other aldehyde functionality showed good stability
under such conditions. The second major reaction for THF ring formation was
achieved by oxidation of 185 with the Co(II) complex. Sonogashira coupling of
187 with 188, followed by couple routine transformations, completed the synthesis
of mucocin smoothly.
The shortest route to mucocin to date was achieved by Evans et al. (Scheme 10-32) 83 ;
ring closing metathesis was elegantly used as a key step. In the presence of
InBr 3 and tert-butyldimethylsilane, a reductive cyclization of 190 was achieved,