RECENT PROGRESS ON THE CHEMICAL SYNTHESIS OF ANNONACEOUS ACETOGENINS AND THEIR STRUCTURALLY MODIFIED MIMICS - Medicinal Chemistry of Bioactive Natural Products - page 412

high selectivity. The Nozaki-Hiyama-Kishi reaction of aldehyde 75 (derived from
74) with vinyl iodide 77, followed by oxidation of the hydroxyl group, selective
hydrogenation of the double bond, and deprotection of the O-TBS ethers, estab-
lished the skeleton and finally afforded 78 (mosin B). In the meantime, the other
isomer 79 was prepared from ent-71. Although both sets of NMRs of 78 and 79
are the same as those of the natural product, the rotation value comparisons sug-
gests that natural mosin B is compound 78.
As in the case of mosin B, the absolute configuration of cis-solamin (the relative
configuration is threo-cis-threo) was also confirmed by total synthesis and compar-
ison of rotations. Both Makabe et al. 44 and Cecil and Brown 45 finished its synthesis
independently (Scheme 10-16). In the route developed by Makabe et al., 44 the cis-
THF-containing compound 81 was prepared from olefin 80, using TBHP-VO
(acac) 2 -mediated epoxidation and an in situ intramolecular epoxide opening as
key reactions. Coupling of alkyne 81 with vinyl iodide 82, selective hydrogenation
of double/triple bonds, and b-elimination to form unsaturated lactone provided
cis-solamin. Cecil and Brown's protocol 45 used a chiral auxiliary to control the

stereochemistry of KMnO 4 -mediated 1,5-diene oxidation, which afforded

A: Makebe's synthesis

OH

TBHP-VO(acac) 2

C 12 H 25

C 12 H 25

O (CH 2 Cl) 2 , 4A MS

MOMO

RO

OMOM 80

R = H
R = MOM

81a

SPh 81b

SPh

+ I

I I

O

O

82

O

O

C 12 H 25 O

O

HO

HO O

threo-cis-threo cis -solamin

B: Brown's synthesis

O

KMnO 4 , AcOH

C 12 H 25

N

O

Adogen, EA

C 12 H 25 N

OS
O

HO

HO S

O

83

84

O

O

OH

EtO 2 C

86

C 12 H 25

cis -solamin

O ( ) 9

Alder-ene

HO

HO

85

Scheme 10-16. Total synthesis of cis-solamin by Makebe et al. and Cecil and Brown.