α-heterosubstituted aldehydes in organic synthesis. Enantioselective approaches to new analogues of mevinic acids

Article abstract of DOI:10.1135/cccc20030975

Various aldol approaches towards the asymmetric synthesis of the lactone moiety of HMG-CoA-reductase inhibitors are described. Auxiliary controlled as well as catalytic aldol reactions resulted only in modest to low selectivities, whereas 1,2-additions to readily available highly enantiomerically enriched α-heterosubstituted aldehydes yielded δ-hydroxy-β-ketoesters with a high degree of diastereocontrol and in good chemical yields. The novel mevinic acid analogues could then be obtained by syn-reduction of the addition products.

Full text of DOI:10.1135/cccc20030975

New Analogues of Mevinic Acids
975
␣-HETEROSUBSTITUTED ALDEHYDES IN ORGANIC SYNTHESIS.
ENANTIOSELECTIVE APPROACHES TO NEW ANALOGUES
OF MEVINIC ACIDS
1,
2
Dieter ENDERS * and Frank BURKAMP
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule,
1
Professor-Pirlet-Straße 1, D-52074 Aachen, Germany; e-mail: enders@rwth-aachen.de,
2
frank_burkamp@merck.com
Received Jan uary 6, 2003
Accepted Jan uary 30, 2003
Dedicated to the memory of Professor Otakar Červinka, a pioneer in asymmetric synthesis and a good
friend.
Various aldol approach es towards th e asym m etric syn th esis of th e lacton e m oiety of
HMG-CoA-reductase in h ibitors are described. Auxiliary con trolled as well as catalytic aldol
reaction s resulted on ly in m odest to low selectivities, wh ereas 1,2-addition s to readily avail-
able h igh ly en an tiom erically en rich ed α-h eterosubstituted aldeh ydes yielded δ-h ydroxy-
β-ketoesters with a h igh degree of diastereocon trol an d in good ch em ical yields. Th e n ovel
m evin ic acid an alogues could th en be obtain ed by syn-reduction of th e addition products.
Keyw ord s: Aldol reaction s; Am in o aldeh ydes; Mukaiyam a reaction ; Stereoselective reaction s;
Asym m etric syn th esis; TADDOL; SAMP; Lacton es; HMG-CoA-reductase in h ibitors.
Sin ce th e lin k between abn orm ally h igh levels of plasm a ch olesterol (i.e.
LDL) an d coron ary h eart disease is well establish ed, th e search for n ew
drugs to treat h yperch olesterolem ia an d ath erosclerosis is an on goin g field
of ph arm aceutical in terest1. Th e followin g approach es to affect plasm a ch o-
lesterol are curren tly bein g pursued: First: keepin g a strict diet, th us affect-
in g th e exogen ic ch olesterol taken up by n utrien ts. Secon d: an tagon isin g
th e in vivo biosyn th esis of en dogen ic ch olesterol, wh ich represen ts up to
70% of body ch olesterol.
Th e com plex en dogen ic path way in volves am on g oth ers th e followin g
th ree key en zym es: HMG-CoA reductase (HMGR)2, squalen e syn th ase
(SQS)3 an d squalen e epoxidase (SQE)4. Furth erm ore, m ost recen tly in terest
h as been focused on th e activity of certain plasm a factors (i.e. ch olesterol
ester tran sfer protein CETP an d ph osph olipid tran sfer protein PLTP)5 be-
Collect. Czech. Chem. Commun. (Vol. 68) (2003)
doi:10.1135/cccc20030975

976
Enders, Burkamp:
cause of th eir ability to con trol th e crucial size distribution of lipoprotein s,
th us affectin g th e ratio of LDL to HDL in th e plasm a.
Alth ough HMGR in h ibitors (statin s) are still provin g to be th e m ost clin i-
cally effective th erapeutic agen ts in th e treatm en t of h yperch olesterolem ia
(e.g. Mevacor, Lipitor an d Crestor), on e h as to keep in m in d th at in h ibition
of ch olesterol biosyn th esis at an early stage also affects oth er biologically
im portan t path ways. Furth erm ore, apart from th e side effects observed with
Baycol in th e clin ic, wh ich led to its with drawal from th e m arket, on ly few
side effects like h yperten sion 6 an d m yopath y7 as well as apoptosis of rat
h epatocytes8 are kn own to date.
Sin ce th e lacton e portion of syn th etic HMGR in h ibitors like Fluvastatin 9
exh ibit on ly two stereogen ic cen ters, exten sive syn th etic studies h ave been
carried out con cern in g m eth odology to gen erate th is fragm en t in en an tio-
m erically pure form 10
.
In th e presen t paper we wish to describe in detail our efforts to syn th esise
th e lacton e part of HMGR in h ibitors via various asym m etric aldol ap-
proach es11.
Auxiliary Controlled Asymmetric Aldol Reactions
At th e begin n in g of our studies we in ten ded to build up th e lacton e portion
of HMGR in h ibitors via a diastereoselective aldol approach 12 usin g various
en an tiopure h ydrazin e an d am in e auxiliaries13 as sh own in Sch em e 1.
Th us, en an tiopure m eth yl acetoacetate derivatives14 1a were depro-
ton ated, em ployin g lith ium 2,2,6,6-tetram eth ylpiperidide (LTMP), an d
subsequen tly reacted with various aldeh ydes. Exten sive optim isation s in volv-
in g inter alia solven t effects, use of various oth er bases as well as additives,
reaction tem perature an d duration were pursued, an d we observed, after
h ydrolytic cleavage of th e auxiliary (SAMP; R1, R2 = H, R3 = H, R4 = Me),
en an tioselectivities of th e correspon din g tetrah ydropyran -2,4-dion es 2 in
th e ran ge of 0 to 58% ee, depen din g stron gly on th e steric bulk of th e alde-
h yde (R = t-Bu, 58% ee; R = i-Pr, 10% ee; R = Bu, 0% ee). Furth erm ore, th e
m eth oxym eth yl-side ch ain of th e ch iral auxiliary seem s to h ave exh ibited
optim al ch elation abilities. Exch an gin g th e m eth yl eth er to th e free alcoh ol
(R4 = H) or a silyl eth er (R4 = tert-butyldim eth ylsilyl) as well as in troducin g
m ore steric bulk in to th e side ch ain (R3 = Me, Et) resulted in a sh arp
decrease in selectivity. It is interesting to note in this context that in pyruvate-
aldol reaction s excellen t selectivities were obtain ed with SAEP (R1, R2 = H,
R3 = Et, R4 = Me) as th e ch iral auxiliary13b. However, th ere is n o such tren d
in β-ketoester aldol reaction s. In case of th e syn th etically m ore im portan t
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
977
dih ydrocin n am on aldeh yde (R = Ph CH2CH2) it turn ed out, th at th e m axi-
m um value of 33% ee was foun d for (R,R,R)-1-am in o-2-(m eth oxym eth yl)-
1-azabicyclo[3.3.0]octan e (R1, R2 = –(CH2)3–, R3 = H, R4 = Me) as ch iral auxil-
iary15. Th is result clearly in dicates th at steric bulkin ess on th e d-face of th e
pyrrolidin e rin g by rin g fusion of a cyclopen tan e m oiety h as a ben eficial
effect to th e diastereoselectivity of th e aldol addition 16. In terestin gly,
ch an gin g th e au xiliary from SAMP to (S,S)-1-am in o-2,5-bis(m eth oxy-
m eth yl)piperidin e (C2-sym m etry of the auxiliary) only resulted in a decreased
selectivity.
Diastereoselective aldol reactions
1. 2.5 LTMP, THF
O
R*
2. RCHO
3. H3O+
NH
O
A
*
H3C
OCH3
R
O
O
38–77%
1a
2
ee = 0–58%
R1
OR4
R3
R2
R* =
N
R3
1. 2 LTMP, 2 TMEDA, THF
2. RCHO
3. H3O+
NR2*
OH
*
O
B
CO2Me
H3C
R
3
MeO
1b
O
11–52%
ee = 10–36%
CH3
Ph
OMe
and
NR2* =
R3
N
HN
R3
SCHEME 1
Em ployin g ch iral secon dary am in es as auxiliaries13d–13h (Sch em e 1), th e
aldol reaction of th e correspon din g m etallated en am in es 1b proceeded
without concom itant lactonisation, resulting in δ-hydroxy-β-ketoesters 3 with
en an tioselectivities in th e ran ge of ee = 0% (R = Bu) to ee = 36% (R = t-Bu).
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

978
Enders, Burkamp:
Th e use of 2 equivalen ts LDA proved to be essen tial to gain m axim um se-
lectivity wh ereas on ly m odest ch em ical yields (20–67%) due to retro-aldol
reaction s could be obtain ed. SMP (R3 = H) yielded th e best ee value,
wh ereas an in creasin g steric dem an d in th e side ch ain (R3 = Me, Et) resulted
in lower en an tioselectivities again (see above; ee = 10 an d 0%, respectively)
in case of pivalaldeh yde. In terestin gly in th is con text, workin g on propio-
n ate aldol reaction s, Sch lessin ger et al. h ave described excellen t diastereo-
selectivities by usin g th e n on -ch elatin g 2,5-dim eth ylpyrrolidin e as th e ch iral
auxiliary13g. Fin ally, usin g th e con dition s in Sch em e 1B, (R)-(+)-1-ph en yl-
eth ylam in e yielded m axim um selectivities of 56% ee in case of th e
sterically m ost dem an din g pivalaldeh yde (R = t-Bu), wh ereas dih ydro-
cin n am on aldeh yde (R = Ph CH2CH2) on ly resulted in 5% en an tio-
selectivity.
Furth er experim en ts in cluded th e use of titan ium an d boron en olates
(TiCl4/NEt3, Cy2BCl/NEt3), as well as silylketen e acetals (TBSOTf/LDA), but
n o sign ifican t im provem en t in selectivity could be n oted.
Asymmetric Aldol Reactions Using Chiral Titanium Complexes
In th e n ext part of our in vestigation we assessed th e possibility of en an tio-
selective aldol reaction s17, usin g ach iral acetoacetate-d4-reagen ts an d ch iral
titan ium com plexes18 in two differen t m an n ers (Sch em e 2).
En an tiopure tartarate-based diols (R,R)-6 (taddols19a–19c) as well as am in o
alcoh ols13b (S)-7 based on prolin e were prepared an d con verted in to th e
correspon din g ch lorotitan ium com plexes19c to be em ployed in tran s-
m etallation s of th e lith ium en olate of en am in oester20 4. Successive aldol re-
action with ben zaldeh yde yielded β-en am in opyran -2-on es 5 with on ly low
en an tioselectivities (ee = 0–12%). Best results were obtain ed usin g tetra-
ph en yltaddol (R,R)-6 (R1 = Ph , 10% ee) an d SDP (S)-7 (R1 = Me, 12% ee).
Furth erm ore, th e Mukaiyam a aldol reaction of dien e21 8 with various al-
deh ydes usin g ch iral titan ium com plexes based on tetraph en yltaddol
(R,R)-6 resulted in δ-h ydroxy-β-ketoesters 3 again with m odest selectivities.
In terestin gly, in th e case of h ydrocin n am aldeh yde ee = 30% was observed,
wh ereas for sterically m ore h in dered aldeh ydes like pivalaldeh yde an d
ben zaldeh yde m ostly cycloarom atisation of th e startin g dien e was observed
an d n o aldol addition product could be detected. Despite furth er opti-
m isation s like ch an gin g th e m ode of addition an d addin g tertiary am in e
bases, we were un able to ch an ge th e outcom e of th e reaction .
Th e recen t success of Carreira et al.17d,18f, Sato et al.18k an d Keck et al.18n
based on th e use of catalysts with Sch iff base an d bin aph th ol ligan ds sh ows
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
979
th at fin e tun in g of th e substitution pattern as well as th e don or properties
proved to be essen tial for effective asym m etric catalysis of m eth yl aldol re-
action s.
Enantioselective aldol reactions
O
O
N
1. 1.1 LDA, THF
N
2. TiCl(Oi-Pr)Y*
3. RCHO
A
*
H3C
R
O
O
12–37%
5
MeO
O
4
ee = 0–12%
R1 R1
O
O
Me
Me
OH
OH
R1
R1
and
Y* =
N
H
OH
R1
R1
6
7
1. RCHO, DCM
2. TiCl2Y*
TMSO
OTMS
OH
*
O
B
CO2Me
OCH3
R
3
8
25–85%
Me Me
ee = 0–30%
O
Me
Me
OH
OH
Y* =
O
Me Me
6
SCHEME 2
Synthesis of α-Heterosubstituted Carbonyl Compounds and Application
to the Synthesis of Novel Mevinic Acid Analogues
After th e failure of th e asym m etric con trol of m eth yl aldol reaction s, we fi-
n ally surveyed th e possibility of in troducin g th e ch irality in form ation in to
th e aldeh yde com pon en t22–24 9 an d reactin g th em with ach iral aceto-
acetate-d4-reagen ts. Th e successive syn-reduction of δ-h ydroxy-β-ketoester
10 accordin g to Sch em e 3 sh ould yield n ovel m evin ic acid an alogues 11
with poten tially n ew biological properties in a h igh ly diastereo- an d
en an tioselective m an n er.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

980
Enders, Burkamp:
On th e oth er h an d, th e h eterosubstituen t X (X = SiR3, NR2, SR) m ay be
furth er m an ipulated in fun ction al group in tercon version s as well as in cou-
plin g reaction s, th us offerin g a broad syn th etic scope.
Diastereoselective 1,2-additions to chiral aldehydes
O
OH
O
OH OH
+ 8
R
R
CO2Me
R
CO2Me
H
syn-
reduction
aldol
X
X
X
11
10
9
X = SR, NR2, SiR3
SCHEME 3
As we23a,24b an d Reetz et al.22f h ave in depen den tly described, optically
active α-h eterosubstituted aldeh ydes (X = NR2, SR, SiR3 an d oth ers) can be ef-
ficien tly prepared usin g eith er th e SAMP/RAMP m eth odology or an ex-ch iral
pool approach .
Followin g th e preceden t of Reetz et al., we obtain ed α-(diben zylam in o)-
substituted aldeh ydes in th ree steps with n o racem isation (Table I) from
com m ercial α-am in o acids. On th e oth er h an d, th e SAMP/RAMP m eth odol-
ogy proved to be th e on ly versatile tool so far to gen erate α-h etero-
TABLE I
Syn th esis of α-(diben zylam in o)-substituted aldeh ydes
Aldeh yde
R
X
ee, %
(S)-9a
(S)-9b
(S)-9c
(S)-9d
(S)-9e
(S)-9f
(S)-9g
(S)-9h
(S)-9i
(S)-9j
(S)-9k
(S)-9l
i-Pr
t-Bu
Bn
NBn 2
NBn 2
NBn 2
NBn 2
TBDMS
TBDMS
St-Bu
St-Bu
St-Bu
St-Bu
SPh
≥96
≥96
≥96
≥96
95
i-Bu
Bn
DCBn a
≥92
91
Pr
i-Pr
Bn
DCBn a
91
93
94
Bn
37b
84b
i-Pr
SPh
a
b
DCBn = 2,4-dich loroben zyl; exten sive racem isation durin g flash ch rom atograph y.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
981
substituted carbon yl com poun ds in a h igh ly en an tioselective m an n er. To
th is en d we were able to exten d th e m eth odology to h eteroatom s such as
sulfur23a, n itrogen 25a, oxygen 25b, ph osph orous26, silicon 24b an d fluorin e27
.
Depen din g on th e tactics em ployed, both an tipodes can be obtain ed with
equal optical purity by usin g on ly SAMP as ch iral auxiliary. In th e outlin ed
publication we on ly followed th e alkylation m eth odology, in corporatin g
silicon an d sulfur as h eteroatom s. Th us, 2-h eterosubstituted aldeh yde-
SAMP h ydrazon es (X = SiR3, SR) were diastereoselectively alkylated followed
by an oxidative cleavage of th e ch iral auxiliary to yield α-h eterosubstituted
aldeh ydes (S)-9a–(S)-9l in en an tiom erically en rich ed form 23a,24b,28 (Table I).
2-Ph en ylsulfan yl substituted aldeh ydes like (S)-9k an d (S)-9l proved to be
h igh ly pron e to racem isation , ren derin g it n ecessary to perform th e purifi-
cation by flash ch rom atograph y as quickly as possible.
Usin g (S)-2-(diben zylam in o)-4-m eth ylpen tan al ((S)-9d ) an d various aceto-
acetate-d4-reagen ts, we optim ised th e aldol reaction con dition s as sh own in
Table II. Th e in itial addition of en am in oester 4 resulted after aqueous
work-up in th e form ation of th e correspon din g γ-en am in odih ydropyran -
5-on e 5 (Sch em e 2A) in on ly low ch em ical yield (m ostly retro-aldol reac-
tion ) an d with n o diastereocon trol. Th e dian ion of m eth yl acetoacetate
yielded δ-h ydroxy-β-ketoester 10d (Table II, en try 2) with 33% de in favour
of th e anti-addition product. Th ese results could be furth er im proved by
em ployin g Mukaiyam a aldol reaction con dition s for dien e 8 (Sch em e 2B
an d Table II, en tries 3–5). Th e sim ultan eous addition of 2.1 equivalen ts of
titan ium tetrach loride an d th e aldeh yde to 3 equivalen ts of th e dien e 8 at
TABLE II
Con dition s of aldol reaction
Acetoacetate-
-d4-reagen t
Yield,
%
dea
%
En try
Equivalen ts
Con dition s
1
2
4
1.0
1.0
LDA, THF, –78 °C
4b
0
m eth yl-
acetoacetate
NaH, BuLi, THF, –78 °C
80c
33
3
4
5
8
8
8
1.0
1.0
1.0
1.2 TiCl2(Oi-Pr)2, DCM, –78 °C
1.0 TiCl4, DCM, –78 °C
6c
33c
60c
≥96
≥96
97
2.1 TiCl4, DCM, –78 °C
a
b
c
Determ in ed by 13C NMR; γ-en am in odih ydropyran -2-on e; δ-h ydroxy-β-ketoester.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

982
Enders, Burkamp:
–78 °C turn ed out to be h igh yieldin g (54–87%) with excellen t diastereo-
selectivities (de > 96%).
Em ployin g th ese reaction con dition s to various en an tiom erically en -
rich ed aldeh ydes, we were able to gen erate a broad ran ge of δ-h ydroxy-
β-ketoesters 10 with h igh diastereoselectivities an d virtually n o loss of
en an tiom eric purity (Table III).
TABLE III
Preparation of δ-h ydroxy-β-ketoesters 10
TMSO
OTMS
OCH3
OH
O
O
2.1 TiCl4, CH2Cl2
+
3
R
CO2Me
R
H
X
X
9
8
10
Hydroxyester 10
Aldeh yde R, X
Yield, %
dea, %
eeb, %
(R,S)-10a
(R,S)-10b
(R,S)-10c
(R,S)-10d
(R,S)-10e
(R,S)-10f
(R,S)-10g
(R,S)-10h
(R,S)-10i
(R,S)-10j
i-Pr, NBn 2
t-Bu, NBn 2
Bn , NBn 2
60
71
71
70
54
60
88
76
87
81
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
≥96
93
i-Bu, NBn 2
Bn , TBDMS
DCBNc, TBDMS
95
Pr, St-Bu
91
i-Pr, St-Bu
91
Bn , St-Bu
DCBn c, St-Bu
93
94
a
b
Determ in ed by 13C NMR; determ in ed by 1H NMR usin g (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoro-
c
eth an -1-ol as ch iral cosolven t (6 equiv.); DCBn = 2,4-dich loroben zyl.
As an altern ative m eth odology we reacted th e keten e acetal29 8 in
Mukaiyam a aldol reaction s usin g BF3·OEt2 an d α-sulfen ylated aldeh ydes to
isolate th e correspon din g anti-addition products (R,S)-13 after flash ch ro-
m atograph y. Herein we observed a crucial depen den ce of th e diastereo as
well as th e en an tio con trol on th e group on sulfur (Tables I an d IV).
In a sim ilar study on 1,2-addition s to racem ic α-sulfen ylated aldeyh des
An n un ziata et al.23c foun d, th at diastereoselectivities depen ded on th e
Lewis acid an d on th e group of sulfur em ployed. Th ey described h igh est
anti-selectivities usin g boron trifluoride eth erate wh ereas titan ium tetrach lo-
ride resulted in lower syn- (S-i-Pr) or anti-selectivities (SPh ).
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New Analogues of Mevinic Acids
983
TABLE IV
Degrees of anti-selectivity of α-h eterosubstituted aldeh ydes29
O
O
OH
O
O
O
1.1 BF3·OEt2, CH2Cl2
+
1.1
R
R
OTMS
O
H
X
X
9
8
13
Hydroxylacton e
R, X
Yield, %
de, %
ee, %
(R,S)-13i
(R,S)-13l
Bn , St-Bu
86
89
92
52
93
80a
i-Pr, SPh
a
Exten sive racem isation of th e aldeh yde durin g work-up.
On th e oth er h an d, Sato et al.29b studied th e diastereoselective addition s
of dien e 8 to α-(ben zyloxy)-substituted aldeh ydes an d th ey h ave foun d
h igh syn-selectivities usin g titan ium tetrach loride as th e Lewis acid.
Lookin g at our results, we were pleased to fin d h igh anti-selectivities
th rough out th e wh ole ran ge of α-h eterosubstituted aldeh ydes with tita-
n ium tetrach loride as th e Lewis acid (Table III). Th e Grun well protocol29,
h owever, did n ot result in equally con sisten t degrees of anti-selectivity
(Table IV). We th erefore con clude th at th e selectivity is determ in ed solely
by th e ch elation abilities of th e h eterosubstituen t an d n ot by th e Lewis acid
em ployed.
TABLE V
Preparation of syn-3,5-dih ydroxyesters (S,R,S)-11
syn-Dih ydroxyester
Yield, %
dea, %
ee, %
(S,R,S)-11a
(S,R,S)-11b
(S,R,S)-11c
(S,R,S)-11e
(S,R,S)-11f
(S,R,S)-11i
(S,R,S)-11j
67
51
61
55
52
78
86
≥96
≥96
≥96
≥96
≥96
80b
80b
≥96
≥96
≥96
93
95
93
94
a
b
In crude product determ in ed by 13C NMR; after recrystalisation from pen tan e determ in ed
by 13C NMR.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

984
Enders, Burkamp:
With th e δ-h ydroxy-β-ketoesters (R,S)-10 in h an d, we th en perform ed th e
syn-reduction of th e keton e m oiety. Th e con dition s of Narasaka et al.30a
,
later m odified by Sletzin ger et al.30b, foun d widespread application s in th e
literature an d proved to be a powerful tool to in troduce th e required syn-diol
fun ction ality.
Th us, treatm en t of th e δ-h ydroxy-β-ketoesters with 1.2 equivalen ts of
tributylboran e an d catalytic am oun ts of pivalic acid in tetrah ydrofuran fol-
lowed by addition of 1.5 equivalen ts of sodium boroh ydride an d m eth an ol
yielded th e correspon din g syn-3,5-dih ydroxyesters (S,R,S)-11 in good ch em -
ical yields (Table V).
Determination of the Relative Configuration
Th e fin al con firm ation of th e relative con figuration was con ducted via two
altern ative procedures.
On th e on e h an d δ-h ydroxy-β-ketoester (R,S)-10d (de = 33% an d de ≥
96%) was cyclised to afford (S,R)-14d followed by selective O-m eth ylation
to yield 4-m eth oxy-5,6-dih ydropyran -2-on e (S,R)-15d (Sch em e 4)
O
O
Me2SO4,
acetone
OH
O
O
O
NaH
THF
CO2Me
OH
OMe
76%
86%
NBn2
NBn2
NBn2
(R,S)-10d
(S,R)-14d
(S,R)-15d
SCHEME 4
Sch em e 5 illustrates th e Newm an projection s alon g th e CH(O)–CH(N)
bon d of both diastereom ers of 15d an d sum m arises th e observed 1H-1H
1
couplin g con stan ts as well as th e observed NOEs of th e H NMR spectrum .
Th e m ore abun dan t diastereom er (S,R)-15d is ch aracterised by a sm all J3,4
couplin g con stan t of 5.2 Hz as well as a relatively sm all NOE between H3
an d H4 (7%). Th ese fin din gs in dicate an equilibrum of gauche-con form er A
an d anti-con form er B, wh ich is furth er m an ifested by a stron g NOE between
H4 an d H2 as well as between H4 an d H2ax. Th e less abun dan t diastereom er
eq
3
exh ibits a sim ilar J couplin g con stan t of 4.1 Hz, but it clearly differs from
th e form er isom er by a stron g NOE (15%) between H3 an d H4, as well as a
sm all effect between H4 an d H2 an d n o detectable effect between H4 an d
eq
H2ax. Con sequen tly, it em erges th at th e relative stereoch em istry of th e m ore
abun dan t stereoisom er is anti.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
985
major isomer (anti): J
3,4
= 5.2 Hz
A
B
(S,R)-15d
minor isomer (syn): J
= 4.1 Hz
3,4
(S,S)-15d
SCHEME 5
To apply a sim ilar argum en t for 1,3-dioxin -4-on e (R,S)-13i, it was con -
verted in to 4-m eth oxydih ydropyran -2-on e (S,R)-16i accordin g to Sch em e 6.
1
Th e H NMR spectra as well as NOE differen ce spectra can be explain ed us-
in g th e Newm an projection s in Sch em e 7.
O
1. MeOH, K2CO3
2. NaOH, THF
3. Me2SO4, acetone
OH
O
O
O
Ph
O
Ph
OMe
StBu
(R,S)-13i
StBu
(S,R)-16i
SCHEME 6
A
B
(S,R)-16i
SCHEME 7
3
Most n otably, th e sm all J couplin g con stan t between H4 an d H5 (6.5 Hz)
as well as th e fact th at n o substan tial NOE between th em could be detected,
leads to th e con clusion th at both con form ers (anti-A an d gauche-B) in
Sch em e 7 h ave to be con sidered. Furth er eviden ce for anti-A is th e fact th at
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

986
Enders, Burkamp:
on ly H5 exh ibits a relatively sm all effect to H3 but n o detectable NOE to
ax
H3eq. Fin ally gauche-B explain s th e NOE of H6 an d H3eq, wh ereas n o effect
can be detected between H6 an d H3
.
ax
Furth erm ore, acetalisation of th e syn-dih ydroxyesters (S,R,S)-11 usin g
2,2-dim eth oxypropan e an d BF3·OEt2 in CH2Cl2 yielded th e correspon din g
1,3-dioxan es (S,S,R)-17, of wh ich th e relevan t 13C NMR reson an ces are
sh own in Table VI.
TABLE VI
Yields an d 13C NMR reson en ces of th e correspon din g 1,3-dioxan es (S,S,R)-17
1,3-Dioxan e
Yield, %
C-1(δ, ppm )
C-2(δ, ppm )
C-3(δ, ppm )
(S,S,R)-17a
(S,S,R)-17b
(S,S,R)-17c
(S,S,R)-17e
(S,S,R)-17f
(S,S,R)-17l
(S,S,R)-17j
55
68
81
90
90
83
67
66.49
67.80
66.26
66.21
66.17
66.24
66.24
19.21
19.12
19.67
19.68
19.61
19.73
19.66
30.03
30.08
30.02
29.99
29.99
29.96
29.81
Sch em e 8 illustrates th e 1H NMR data (3J4,5 = 2.7 Hz) as well as th e ob-
served NOEs of 1,3-dioxan e (S,S,R)-17e. Most n otable is th e relatively stron g
NOE between H4 an d H5 (14%) as well as th e sm aller on es between H5 an d
H3 (3%) an d between H5 an d H3 (6%). Th ese fin din gs clearly prove th e
eq
ax
gauche orien tation of H4 an d H3 as well as th e (S,S,R) con figuration as
sh own .
(S,S,R)-17e
SCHEME 8
A sim ilar argum en t con cern in g 1,3-dioxan e (S,S,R)-17j leads to a discus-
sion of both gauche-con form ers A an d B (3J4,5 = 5.4 Hz; substan tial NOE be-
tween H4 an d H5) sh own in Sch em e 9. Con form er A accoun ts for th e sm all
NOE between H6 an d H5 as well as H6 an d H3 an d explain s th e absen ce of
ax
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
987
an y detectable effect between H3 an d H6′. Furth erm ore, th e stron g effect
ax
between H7 an d H6′ an d th e lack of a m easurable effect between H7 an d H6
as well as th e substan tially stron ger NOEs of H5 to H3 as com pared to H3
eq
ax
is clearly explain ed by con form er gauche-A.
A
B
(S,S,R)-17j
SCHEME 9
On th e oth er h an d in volvem en t of con form er B accoun ts for th e sm all ef-
fect between H4 an d H6 as well as H4 an d H6′. Fin ally, th ere is on ly a sm all
effect between H6′ an d H3 an d n o m easurable effect of H6′ an d H3
.
ax
eq
In sum m ary, th ese fin din gs again accoun t for th e (S,S,R) con figuration .
Conclusions
In th e presen t study we un equivocally proved th e followin g poin ts: First,
α-h eterosubstituted aldeh ydes, gen erated efficien tly by th e SAMP m eth od-
ology, can be effectively em ployed in Mukaiyam a aldol addition s resultin g
in excellen t anti-selectivities an d good ch em ical yields. Secon d, th e gen er-
ated syn-dih ydroxyesters are a n ew en try in to a n ovel class of HMGR in h ibi-
tors bein g accessible in two steps in diastereo- an d en an tiopure form .
EXPERIMENTAL
All reaction s were carried out usin g stan dard Sch len k tech n iques un less oth erwise stated.
Solven ts were dried an d purified by con ven tion al m eth ods prior to use. Tetrah ydrofuran an d
dieth yl eth er were fresh ly distilled from potassium , dich lorom eth an e from CaH2 un der ar-
gon . Ligh t petroleum refers to th e fraction with a boilin g ran ge of 40–80 °C. Reagen ts of
com m ercial quality were used from fresh ly open ed con tain ers un less oth erwise stated.
En am in oester 4 was prepared followin g th e preceden t of Ch an et al.20 Th e ch iral
pyrrolidin e based am in es an d h ydrazin es as well as th e correspon din g h ydrazon es an d
en am in es were prepared accordin g to kn own literature preceden ts13b,13i,13j. Th e various
tartarate-based taddolate ligan ds an d th e ch iral titan ium com plexes could be obtain ed ac-
cordin g to Seebach et al.19c Dien es 8 an d 12 were prepared followin g eith er th e two-step
silylation m eth odology21 an d followin g th e protocol of Grun wel et al.29, respectively. Fol-
lowin g th e preceden t of Reetz et al.22f,22i
(S)-9a–(S)-9c. Th e α-silylated an d α-sulfen ylated aldeh ydes (S)-9e–(S)-9l were prepared as re-
cen tly described23a,24b
, we prepared α-(diben zylam in o)aldeh ydes
.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

988
Enders, Burkamp:
An alytical TLC: Merck glass-backed silica gel 60 F254 plates. Preparative colum n ch rom a-
tograph y: Merck silica gel 60, particle size 0.040–0.063 m m (230–400 m esh ) (flash ). An alyti-
cal GC: Siem en s Sich rom at 2 or 3 equipped with a SE-54-CB colum n (25 m × 0.25 m m ),
carrier gas n itrogen , FID. Optical rotation s: Perkin –Elm er P 241 polarim eter; solven ts of Merck
UVASOL quality un less oth erwise stated. Specific rotation s are given in deg cm 3 g–1 dm–1. IR
spectra (ν, cm –1): Perkin –Elm er 1420 an d Perkin –Elm er FT/IR 1750. 1H (300 MHz) an d 13C NMR
spectra (75 MHz) (δ, ppm ; J, Hz): Varian VXR 300 an d Gem in i 300 (solven t: CDCl3, TMS as
in tern al stan dard). Mass spectra: Varian MAT 212 (EI 70 eV) (relative in ten sities in paren th e-
ses). HRMS: Fin n igan MAT 95. Microan alyses: Heraeus CHN-O-Rapid.
Gen eral Procedure for Aldol Reaction of Ch iral Meth yl β-Hydrazon obutan oates 1a
(Procedure I)
A flam e-dried Sch len k flask was purged with n itrogen an d ch arged with 2.5 equiv. of
2,2,6,6-tetram eth ylpiperidin e in THF (4 m l/m m ol). After th e addition of 2.5 equiv. of BuLi
at 0 °C wh ile stirrin g, a golden -yellow solution of LTMP was obtain ed with in 10 m in an d
th e solution was cooled to –78 °C. Th e β-h ydrazon obutan oate 1a was added dropwise an d
th e cool bath rem oved to warm up th e solution to 0 °C. Stirrin g was con tin ued for an oth er
2 h , wh ile a deep oran ge solution was obtain ed. After coolin g down to –95 °C, an aldeh yde
was added slowly dropwise an d th e reaction m ixture was warm ed up overn igh t. Th e reac-
tion was quen ch ed by addition of glacial acetic acid (0.37 m l/m m ol). Extractive work-up
with dieth yl eth er/water (100 m l/10 m l) yielded th e crude γ-h ydrazon opyran s wh ich were
dissolved in dieth yl eth er (20 m l/m m ol). 1.4 M HCl (1 m l/m m ol) was added an d th e result-
in g two-ph ase system was stirred at room tem perature for an oth er 15 h to cleave off th e
ch iral au xiliary. Separation of th e organ ic ph ase an d stan dard extractive work-u p with
dieth yl eth er yielded th e crude γ-ketopyran s 2, wh ich were fin ally purified by colum n ch ro-
m atograph y.
Gen eral Procedure for Aldol Reaction of Ch iral β-En am in obutan oates 1b (Procedure II)
A flam e-dried Sch len k flask was purged with n itrogen an d ch arged with 2.0 equiv.
diisopropylam in e in THF (4 m l/m m ol). After dropwise addition of 2.0 equiv. of BuLi at 0 °C
with stirrin g a ligh t-yellow solution of LDA was obtain ed with in 10 m in . Th e solution was
cooled to –78 °C an d 2.0 equiv. of N,N,N′,N′-tetram eth yleth ylen ediam in e were added
dropwise followed by th e correspon din g β-en am in obutan oate 1b. Stirrin g was con tin ued for
an oth er h our at th at tem perature yieldin g a yellow solution of th e correspon din g en olate.
After coolin g to –95 °C th e aldeh yde was added slowly dropwise an d th e reaction m ixture
was stirred for an oth er h our wh ile warm in g up to –78 °C. Th e reaction was quen ch ed by
addin g glacial acetic acid (0.37 m l/m m ol) an d stan dard extractive work-up with dieth yl
eth er (30 m l/m m ol) an d water (3 m l/m m ol) yielded th e crude β-en am in oester wh ich was
dissolved in dieth yl eth er (20 m l/m m ol). 1.4 M HCl (1 m l/m m ol) was added an d th e result-
in g two-ph ase system was stirred at room tem perature for an oth er 15 h to cleave th e ch iral
auxiliary. Separation of th e organ ic ph ase followed by stan dard extraction work-up with di-
eth yl eth er yielded th e crude δ-h ydroxy-β-ketoesters 3, wh ich were fin ally purified by col-
um n ch rom atograph y.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
989
Gen eral Procedure for Aldol Reaction of En am in oester 4 Usin g Ch iral Titan ium Com plexes
(Procedure III)
A flam e-dried Sch len k flask was purged with n itrogen an d ch arged with 1.1 equiv. of
diisopropylam in e in THF (4 m l/m m ol). At 0 °C 1.1 equiv. of BuLi were added wh ile stirrin g
to yield a ligh t-yellow solution of LDA with in 10 m in . Th e solution was cooled to –78 °C
an d th e β-en am in obutan oate 4 was slowly added. Stirrin g was con tin ued for an oth er h our at
th at tem perature yieldin g a yellow solution of th e correspon din g en olate. Th e correspon din g
titan ium com plex (0.5 M solution in THF) was added at th e sam e tem perature, resultin g in a
dark oran ge solution . After stirrin g for an oth er h our at th e sam e tem perature th e aldeh yde
was added slowly an d th e reaction m ixtu re was allowed to warm u p to room tem pera-
ture overn igh t. Th e reaction was quen ch ed by addin g 20% n eutral aqueous KF solution
(1.0 m l/m m ol) an d stan dard extraction work-up with dieth yl eth er (30 m l/m m ol) an d water
(10 m l/m m ol) yielded th e crude β-en am in oester 5 wh ich was fin ally purified by colum n
ch rom atograph y.
Gen eral Procedure for TiCl4-Mediated Addition of 1-Meth oxy-1,3-bis[(trim eth ylsilyl)oxy]-
butadien e 8 to Ach iral Aldeh ydes Usin g Ch iral Titan ium Catalysts (Procedure IV)
A flam e-dried Sch len k flask was ch arged with a solution of th e correspon din g ach iral alde-
h yde in dich lorom eth an e (10 m l/m m ol) an d cooled to –78 °C. After th e dropwise addition
of th e correspon din g titan ium com plex (0.5 M solution in DCM) th e resultin g com plex pre-
cipitated, yieldin g a ligh t yellow h eterogen ous m ixture. Two equivalen ts of 1-m eth oxy-
1,3-bis[(trim eth ylsilyl)oxy]butadien e 8 dissolved in dich lorom eth an e (1 m l/m m ol) were
added an d stirrin g was con tin ued at th e sam e tem perature for an oth er 2 h . Th e resultin g re-
action m ixture was quen ch ed by addin g dry m eth an ol (1 m l/m m ol) an d poured in to a sepa-
ratin g fun n el. After addition of dieth yl eth er (50 m l/m m ol) an d pH-7 buffer (10 m l/m m ol)
th e organ ic layer was separated an d stan dard aqueous work-up followed by purification us-
in g colum n ch rom atograph y afforded pure δ-h ydroxy-β-ketoesters 3 as colourless oils.
Gen eral Procedure for TiCl4-Mediated Addition of 1-Meth oxy-1,3-bis[(trim eth ylsilyl)oxy]-
butadien e 8 to En an tiom erically En rich ed Aldeh ydes 9 (Procedure V)
A flam e-dried Sch len k flask was ch arged with a solution of 1-m eth oxy-1,3-bis[(trim eth yl-
silyl)oxy]butadien e 8 (2.34 g, 9.0 m m ol) in dich lorom eth an e (30 m l) an d cooled to –78 °C.
After sim ultan eous dropwise addition of th e correspon din g α-h eterosubstituted aldeh yde 9
(3.0 m m ol in 12.4 m l dich lorom eth an e) an d titan ium tetrach loride solution (12.4 m l, c =
0.5 m ol/l in dich lorom eth an e, 6.2 m m ol) via m otorized syrin ge pum ps, th e dark reaction
m ixture was stirred for furth er 30 m in followed by addition of m eth an ol (3 m l). Th e oran ge
m ixture was poured in to a separatin g fun n el followed by dieth yl eth er (300 m l) an d pH-7
buffer (50 m l) an d th e organ ic layer was separated. Th e aqueous layer was extracted twice
with dieth yl eth er (50 m l) an d th e com bin ed organ ic ph ase was wash ed with brin e, dried
over m agn esium sulfate an d filtered. Evaporation of th e solven t in vacuo an d purification by
colum n ch rom atograph y afforded pure h ydroxyesters (R,S)-10 as colourless oils.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

990
Enders, Burkamp:
Gen eral Procedure for BF3 Eth erate-Mediated Addition of 2,2-Dim eth yl-4-m eth yliden e-6-
[(trim eth ylsilyl)oxy]-1,3-dioxin e 12 to α-Alkyl- or α-Arylsulfan ylaldeh ydes (S)-9i an d (S)-9l
(Procedure VI)
A flam e-dried Sch len k flask was ch arged with a solution of th e (S)-9i or (S)-9l (2 m m ol) in
dich lorom eth an e (10 m l) an d cooled to –78 °C. After dropwise addition of boron trifluoride
eth erate (0.62 m l, 4.2 m m ol) an d furth er stirrin g for 10 m in a solution of 2,2-dim eth yl-
4-m eth yliden e-6-[(trim eth ylsilyl)oxy]-1,3-dioxin e 12 (1.07 g, 5 m m ol in 5 m l of dich loro-
m eth an e) was added dropwise. After stirrin g for a furth er 1 h th e oran ge solution was
poured in to a separatin g fun n el followed by dieth yl eth er (50 m l) an d pH-7 buffer (10 m l)
an d th e organ ic layer was separated. Th e aqueous layer was extracted twice with dieth yl
eth er (50 m l) an d th e com bin ed organ ic ph ase was wash ed with brin e, dried over m agn e-
sium sulfate an d filtered. Evaporation of th e solven t in vacuo an d purification by colum n
ch rom atograph y afforded pure h ydroxylacton es (R,S)-13 as colourless oils.
Gen eral Procedure for syn-Reduction of δ-Hydroxy-β-ketoesters 10 (Procedure VII)
A flam e-dried Sch len k flask was ch arged with a solution of tributylboran e (1.1 equiv.) in
THF (10 m l/m m ol) an d a δ-h ydroxy-β-ketoester 10 was added dropwise as a solution in THF
(c = 0.1 m ol/l) at room tem perature. After th e addition of pivalic acid (0.01 equiv.) stirrin g
was con tin ued for an oth er 15 m in an d th e reaction m ixture was subsequen tly cooled to
–95 °C. Sodium boroh ydride (1.5 equiv.) was added in on e portion followed by th e dropwise
addition of dry m eth an ol (0.8 m l/m m ol). After warm in g up to room tem perature overn igh t
th e reaction was quen ch ed by addition of glacial acetic acid (1 m l/m m ol) followed by a
stan dard aqueous work-up with dieth yl eth er. Th e resultin g crude boron ate was sapon ified
by th ree-fold azeotropic distillation usin g m eth an ol (10 m l/m m ol). Th e resultin g sirup was
fin ally purified by colum n ch rom atograph y to afford diols (S,R,S)-11 as colourless oils.
Gen eral Procedure for Lacton isation an d Meth ylation of δ-Hydroxy-β-ketoesters 10
(Procedure VIII)
A roun d bottom ed flask was ch arged with a solution of a h ydroxyester 10 in THF (5 m l/m m ol)
an d 1 M NaOH (1 equiv.) was added dropwise wh ile coolin g in an ice bath . After warm in g
up to room tem perature stirrin g was con tin ued for an oth er 45 m in an d th e reaction m ixture
was subsequen tly acidified with 1 M aqueous h ydroch loric acid. Stan dard aqueous work-up
with dieth yl eth er (30 m l/m m ol) an d water (3 m l/m m ol) resulted in a sirup, wh ich was fi-
n ally purified by colum n ch rom atograph y, an d th e resultin g β-ketopyran on e was dissolved
in aceton e (5 m l/m m ol) usin g a roun d bottom ed flask. Dry potassium carbon ate (2 equiv.)
was added followed by dim eth yl sulfate (1.1 equiv.) an d stirred at room tem perature for
an oth er 12 h . Th e reaction was q u en ch ed by addin g water (5 m l/ m m ol) an d stan dard
extractive work-up with dieth yl eth er (30 m l/m m ol) yielded th e crude 4-m eth oxy-5,6-dih ydro-
pyran -2-on e 15, wh ich was fin ally purified by colum n ch rom atograph y.
Gen eral Procedure for Acetalisation of syn-1,3-Dih ydroxyesters (S,R,S)-11 (Procedure IX)
An oven -dried roun d bottom flask was ch arged with 2,2-dim eth oxypropan e (10 equiv.) in
CH2Cl2 (5 m l/m m ol) an d was cooled to –78 °C. After th e slow addition of boron trifluoride
eth erate (10 equiv.). Stirrin g was con tin ued for an oth er 10 m in an d th e correspon din g diol
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
991
(S,R,S)-11 was added in CH2Cl2 (1 m l/m m ol). Th e reaction m ixture was allowed to warm to
room tem perature over 6 h an d th e resultin g red solution was poured in to a separation fun -
n el followed by dieth yl eth er (100 m l/m m ol) an d water (10 m l/m m ol). Th e organ ic ph ase
was separated an d wash ed with saturated aqueous sodium h ydrogen carbon ate solution an d
brin e an d dried over m agn esium sulfate. After filterin g off th e dryin g agen t an d rem ovin g
th e solven t un der reduced pressure th e rem ain in g sirup was purified by colum n ch rom atog-
raph y to yield th e 1,3-dioxan es (S,S,R)-17 as sirups or solids.
(S)-(–)-2-(tert-Butyldimethylsilyl)-3-(2,4-dichlorophenyl)propanal24b ((S)-9e): 2.5 g (72%) yield
from (S)-(+)-1-{[2-(tert-butyldim eth ylsilyl)eth yliden e]am in o}-2-(m eth oxym eth yl)pyrrolidin e
after colum n ch rom atograph y (silica gel, ligh t petroleum /dieth yl eth er, 4:1); RF 0.78 (ligh t
petroleum /dieth yl eth er, 4:1); [α ]D20 –52.6 (c 1.03, C6H6); ee = 92%, determ in ed after
red u ction an d esterification with (S)-2-m eth oxy-2-ph en yl-3,3,3-trifluoropropan oic acid by
1H NMR. IR (film ): 3380, 3082, 3060, 2945, 2922, 2878, 2852, 2817, 2719, 1925, 1895, 1695
(CO), 1585, 1467, 1440, 1419, 1385, 1362, 1338, 1300, 1280, 1250, 1180, 1099, 1068, 1048,
1007, 947, 863, 850, 830, 819, 770, 703, 689, 669, 658. 1H NMR: 0.14 s, 3 H (H-10); 0.21 s,
3 H (H-10′); 1.00 s, 9 H (H-12); 2.87 dd, 1 H, J(3,3′) = 14.0, J(3,2) = 2.2 (H-3); 3.00 ddd, 1 H,
J(2,3′) = 11.5, J(2,1) = 2.5, J(2,3) = 2.2 (H-2); 3.31 dd, 1 H, J(3′,3) = 14.0, J(3′,2) = 11.5 (H-3′);
7.12 dd, 1 H, J(8,9) = 8.2, J(8,6) = 1.9 (H-8); 7.25 d, 1 H, J(9,8) = 8.2 (H-9); 7.31 d, 1 H, J(6,8) =
1.9 (H-6); 9.64 d, 1 H, J(1,2) = 2.5. 13C NMR: –6.51 (C-10), –6.21 (C-10′), 17.90 (C-11), 26.88
(C-12), 28.20 (C-3), 47.98 (C-2), 126.92 (C-8), 129.13 (C-9), 132.31 (C-6), 132.51 (C-7),
133.94 (C-5), 137.88 (C-4), 201.40 (C-1). MS (70 eV, m/z (rel.%)): 316 (1.1) [M+], 301 (3.5)
[M+ – CH3], 259 (100) [M+ – C4H9], 247 (1.6), 231 (1.8), 223 (3.7), 203 (63), 185 (17.1), 167
(13.7), 159 (9.7) [C7H5Cl2+], 149 (9.4), 131 (6.8), 115 (9.8) [TBDMS+], 105 (13.9), 95 (26.7),
93 (75.3), 75 (50.6) [C2H7SiO+], 73 (67), 59 (27.8), 45 (10) [C3H7+], 43 (8), 41 (7). For
C
15H22Cl2OSi (316.1) calculated: 56.77% C, 6.99% H; foun d: 56.39% C, 7.01% H.
(S)-(–)-2-(tert-Butylsulfanyl)-3-(2,4-dichlorophenyl)propanal23a ((S)-9j): 1.8 g (54%) yield from
(S)-(+)-1-{[2-(tert-butylsulfan yl)eth yliden e]am in o}-2-(m eth oxym eth yl)pyrrolidin e after col-
um n ch rom atograph y (silica gel, ligh t petroleum /dieth yl eth er, 4:1); RF 0.55 (ligh t petro-
leum /dieth yl eth er, 10:1); [α ]2D0 –142.0 (c 1.7, C6H6); ee = 94%, determ in ed after reduction
an d esterification with (S)-2-m eth oxy-2-ph en yl-3,3,3-trifluoropropan oic acid by 1H NMR. IR
(film ): 3402, 3091, 3075, 3035, 2967, 2927, 2862, 2838, 2726, 1709 (CO), 1589, 1562, 1475,
1459, 1436, 1389, 1380, 1367, 1339, 1293, 1256, 1218, 1205, 1172, 1153, 1102, 1073, 1050,
988, 958, 934, 868, 817, 762, 717, 679, 656, 621, 584, 563. 1H NMR: 0.75 s, 9 H (H-11);
2.71 dd, 1 H, J(3,3′) = 14.0, J(3,2) = 7.7 (H-3); 3.08 dd, 1 H, J(3′,3) = 14.0, J(3′,2) = 7.7 (H-3′);
3.38 td, 1 H, J(2,3′) = J(2,3) = 7.7, J(2,1) = 3.0 (H-2); 6.74 d, 1 H, J(9,8) = 8.2 (H-9); 6.80 dd,
1 H, J(8,9) = 8.2, J(8,6) = 2.0 (H-8); 7.12 d, 1 H, J(6,8) = 2.0 (H-6); 9.24 d, 1 H, J(1,2) =
3.0. 13C NMR: 30.83 (C-11), 33.04 (C-3), 44.39 (C-10), 50.75 (C-2), 127.00 (C-8), 129.32
(C-9), 133.47 (C-7), 133.76 (C-6), 134.54 (C-5), 134.98 (C-4), 193.24 (C-1). MS (70 eV, m/z
(rel.%)): 290 (0.4) [M+], 261 (1.6) [M+ – C4H8], 255 (7.9), 199 (7.5), 169 (3.1), 159 (8.4), 134
(2.8), 102 (3.4), 89 (4.7), 57 (100) [C4H9+], 41 (25.3). For C13H16Cl2OS (291.2) calculated:
53.61% C, 5.54% H; foun d: 53.80% C, 5.62% H.
(S)-(–)-2-(Phenylsulfanyl)-3-methylbutanal23a ((S)-9l): 2.3 g (60%) yield from (S)-(+)-1-{[2-(ph en -
ylsulfan yl)eth yliden e]am in o}-2-(m eth oxym eth yl)pyrrolidin e after colum n ch rom atograph y
(silica gel, ligh t petroleum /dieth yl eth er, 4:1); RF 0.69 (ligh t petroleum /dieth yl eth er, 4:1);
[α ]2D0 –26.0 (c 0.95, C6H6); ee = 84%, determ in ed after reduction an d esterification with
(S)-2-m eth oxy-2-ph en yl-3,3,3-trifluoropropan oic acid by 1H NMR. IR (film ): 3413, 3059,
3010, 2963, 2932, 2872, 2812, 2715, 1953, 1879, 1800, 1718 (CO), 1584, 1482, 1467, 1439,
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992
Enders, Burkamp:
1389, 1370, 1340, 1325, 1252, 1189, 1166, 1135, 1089, 1068, 1049, 1025, 1001, 986, 930,
898, 741, 691. 1H NMR: 1.07 d, 3 H, J(4,3) = 6.9 (H-4); 1.18 d, 3 H, J(4,3) = 6.6 (H-4′); 2.09
dqq, 1 H, J(3,2) = 8.5, J(3,4) = 6.9, J(3,4′) = 6.6 (H-3); 3.27 dd, 1 H, J(2,3) = 8.5, J(2,1) = 5.3
(H-2); 7.20–7.40 m , 5 H (H-6, H-7 an d H-8); 9.35 d, 1 H, J(1,2) = 5.3. 13C NMR: 19.99 (C-4),
20.68 (C-4′), 27.85 (C-3), 64.46 (C-2), 127.78 (C-7), 129.14 (C-6), 132.20 (C-8), 132.68 (C-5),
194.96 (C-1). MS (70 eV, m/z (rel.%)): 194 (48.9) [M+], 165 (100) [M+ – CHO], 137 (3.5), 123
(54.5), 109 (18.9), 91 (4.1) [C7H7+], 87 (8.8), 77 (5.5), 55 (46.4), 45 (19.7), 41 (12.5), 39
(15.7). For C11H14OS (194.3) calculated: 68.00% C, 7.26% H; foun d: 68.17% C, 7.28% H.
Methyl (5R,6S)-(+)-6-(dibenzylamino)-5-hydroxy-7-methyl-3-oxooctanoate ((R,S)-10a): 0.85 g
(60%) yield from aldeh yde 9a after colum n ch rom atograph y (silica gel, ligh t petroleum /di-
eth yl eth er, 4:1); RF 0.36 (ligh t petroleum /dieth yl eth er, 2:1) followin g procedure V; [α ]2D0 3.0
(c 1.0, CH2Cl2); de = 97%, determ in ed by NMR; ee > 96%, determ in ed after syn-reduction
an d acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3085,
3062, 3028, 2954, 2836, 2803, 2718, 2208, 1950, 1879, 1747, 1713 (COOCH3), 1654, 1631,
1602, 1568, 1494, 1453, 1438, 1404, 1385, 1362, 1323, 1245, 1208, 1154, 1100, 1070, 1029,
1014, 973, 913, 865, 846, 750, 700. 1H NMR: 1.04 d, 3 H, J(7,8) = 6.6 (H-8); 1.15 d, 3 H,
J(7,8′) = 6.6 (H-8′); 2.20 dsept, 1 H, J(6,7) = 6.9, J(7,8) = 6.6 (H-7); 2.44 dd, 1 H, J(6,7) = 6.6,
J(6,5) = 6.3 (H-6); 2.58 dd, 1 H, J(4,5) = 10.4, J(4,4′) = 16.8 (H-4); 2.90 dd, 1 H, J(4,4′) = 16.8,
J(4′,5) = 1.9 (H-4′); 3.44 d, 1 H, J(2,2′) = 15.7 (H-2); 3.49 d, 1 H, J(2,2′) = 15.7 (H-2′); 3.66 d,
2 H, J(9,9′) = 13.4 (H-9); 3.70 s, 3 H (OCH3); 3.75 d, 2 H, J(9,9′) = 13.4 (H-9′); 4.30 m , 1 H,
(H-5); 7.21–7.36 m , 10 H (H-11, H-12, H-13). 13C NMR: 20.02 (C-8), 23.45 (C-8′), 26.65
(C-7), 47.78 (C-4), 49.75 (C-2), 52.35 (OCH3), 55.37 (C-9), 65.53 (C-6), 66.47 (C-5), 127.19
(C-12), 128.43 (C-11), 129.06 (C-13), 139.60 (C-10), 167.48 (C-1), 203.73 (C-3). MS (70 eV,
m/z (rel.%)): 397 (0.7) [M+], 366 (2) [M+ – OCH3], 354 (6) [M+ – C3H7], 336 (4) [M+ – H2O –
C3H7], 252 (100) [C19H23NO+ – CHO], 181 (9), 91 (89) [C7H7+], 65 (5), 43 (4). HRMS
C
21H24NO4](M+ – C3H7) calculated: 354.1705; foun d: 354.1708.
Methyl (5R,6S)-(–)-6-(dibenzylamino)-5-hydroxy-7,7-dimethyl-3-oxooctanoate ((R,S)-10b): 1.05 g
(71%) yield from aldeh yde 9b after colum n ch rom atograph y (silica gel, ligh t petroleum /
dieth yl eth er, 4:1) followin g procedure V; RF 0.35 (ligh t petroleum /dieth yl eth er, 2:1); [α ]D20
–25.4 (c 1.1, CH2Cl2); de > 96%, determ in ed by NMR; ee > 96%, determ in ed after syn-reduc-
tion an d acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3085,
3063, 3025, 2954, 2911, 2872, 2801, 1950, 1745, 1712 (COOMe), 1654, 1602, 1494, 1453,
1438, 1402, 1359, 1325, 1217, 1154, 1122, 1073, 1028, 962, 918, 852, 757, 701, 668. 1H NMR:
1.08 s, 9 H (H-8); 2.38 d, 1 H, J(5,6) = 4.1 (H-6); 2.76 dd, 1 H, J(4,4′) = 17.9, J(4,5) 8.5 (H-4);
2.83 dd, 1 H, J(4′,4) 17.9, J(4′,5) = 8.2 (H-4′); 3.36 d, 1 H, J(2,2′) = 16.7 (H-2); 3.40 d, 1 H,
J(2,2′) = 16.7 (H-2′); 3.62–3.73 d br, 2 H, J(9,9′) = 13.7 (H-9); 3.75 s, 3 H (OCH3); 3.92–4.13
m br, 2 H (H-9′); 4.49 ddd, 1 H, J(5,4) = 8.5, J(5,4′) = 8.2, J(5,6) = 4.1 (H-5); 7.20–7.36 m , 10 H
(H-11, H-12, H-13). 13C NMR: 29.84 (C-8), 37.63 (C-7), 49.46 (C-4), 50.59 (C-2), 52.44
(OCH3), 56.41 (br, C-9), 67.42 (C-6), 67.48 (C-5), 126.94 (C-12), 128.22 (C-11), 129.35 (br,
C-13), 140.05 (br, C-10), 167.3 (C-1), 204.15 (C-3). MS (70 eV, m/z (rel.%)): 411 (0.2) [M+],
380 (1) [M+ – OCH3], 354 (23) [M+ – C4H9], 336 (2) [M+ – H2O – C4H9], 322 (4) [354+
–
CH3OH], 266 (33) [C20H25NO+ – CHO], 181 (9), 91 (100) [C7H7+], 65 (9), 43 (25) [C3H7+].
HRMS C21H24NO4 (M+ – C4H9) calculated: 354.1705; foun d: 354.1706.
Methyl (5R,6S)-(+)-6-(dibenzylamino)-5-hydroxy-3-oxo-7-phenylheptanoate ((R,S)-10c): 0.94 g
(67%) yield from aldeh yde 9d after colum n ch rom atograph y (silica gel, ligh t petroleum /di-
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New Analogues of Mevinic Acids
993
eth yl eth er, 4:1) followin g procedure V; RF 0.32 (ligh t petroleum /dieth yl eth er, 2:1); [α ]D20
+16.2 (c 1.5, CH2Cl2); de = 97%, determ in ed by NMR; ee > 96%, determ in ed after syn-reduc-
tion an d acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3650–3200, 3084, 3061,
3027, 2953, 2929, 2850, 2804, 1950, 1875, 1810, 1747, 1713 (COOMe), 1654, 1630, 1602,
1494, 1454, 1438, 1404, 1373, 1323, 1249, 1207, 1153, 1121, 1074, 1028, 1020, 974, 909,
858, 746, 700. 1H NMR: 2.44 dd, 1 H, J(7,7′) = 17.6, J(7,6) = 9.9 (H-7); 2.80 s br, 1 H (OH);
2.93 m , 1 H (H-6); 2.97 dd, 1 H, J(7,7′) = 17.6, J(7′,6) = 1.9 (H-7′); 2.99 dd, 1 H, J(4,4′) =
14.1, J(4,5) = 5.7 (H-4); 3.08 dd, 1 H, J(4,4′) = 14.1, J(4′,5) = 7.4 (H-4′); 3.34 d, 1 H, J(2,2′) =
15.7 (H-2); 3.39 d, 1 H, J(2,2′) = 15.7 (H-2′); 3.58 d br, 2 H, J(12,12′) = 13.7 (H-12); 3.70 s, 3 H
(OCH3); 3.73 d br, 2 H, J(12,12′) = 13.7 (H-12′); 4.28 m , 1 H (H-5); 7.13–7.34 m , 15 H (H-9,
H-10, H-11, H-14, H-15, H-16). 13C NMR: 32.29 (C-7), 47.95 (C-4), 49.58 (C-2), 52.39
(OCH3), 54.65 (C-12), 62.92 (C-6), 68.46 (C-5), 125.96 (C-10), 126.99 (C-15), 128.26 (C-9),
128.37 (C-14), 128.83 (C-11), 129.41 (C-16), 139.38 (C-8), 141.00 (C-13), 167.33 (C-1),
203.92 (C-3). MS (70 eV, m/z (rel.%)): 445 (0.1) [M+], 354 (14) [M+ – C3H7], 336 (2) [354 –
H2O], 322 (3) [354 – CH3OH], 300 (66) [C22H22N+], 181 (6), 132 (2), 92 (8), 91 (100) [C7H7+],
65 (5), 44 (4.0). For C28H31NO4 (445.6) calculated: 75.48% C, 7.01% H, 3.14% N; foun d:
75.38% C, 7.33% H, 3.57% N.
Methyl (5R,6S)-(–)-6-(dibenzylamino)-5-hydroxy-8-methyl-3-oxononanoate ((R,S)-10d ): 0.86 g
(70%) yield from aldeh yde 9d after colum n ch rom atograph y (silica gel, ligh t petroleum /di-
eth yl eth er, 4:1) followin g procedure V; RF 0.32 (ligh t petroleum /dieth yl eth er, 1:2); [α ]D20
–1.8 (c 1.1, CH2Cl2); de = 95%, determ in ed by NMR; ee > 96%, determ in ed by 1H NMR with
(–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ):
3700–3200 (OH), 3086, 3062, 3029, 2953, 2866, 2841, 2804, 1955, 1855, 1747 (COOMe),
1713 (COOMe), 1654, 1603, 1513, 1494, 1453, 1438, 1405, 1384, 1367, 1322, 1245, 1217,
1209, 1157, 1105, 1068, 1028, 966, 918, 849, 749, 700, 681. 1H NMR: 0.77 d, 3 H, J(9,8) =
6.3 (H-9); 0.92 d, 3 H, J(9′,8) = 6.6 (H-9′), 1.28 ddd, 1 H, J(7,7′) = 14.0, J(7,6) = 6.9, J(7,8) =
6.5, 1 H (H-7); 1.65 ddd, 1 H, J(7,7′) = 14.0, J(7′,8) = 6.9, J(7′,6) = 6.5, 1 H (H-7′); 1.86 m , 1 H
(H-8); 2.55 dd, 1 H, J(4,4′) = 17.0, J(4,5) = 9.6, 1 H (H-4); 2.58 ddd, 1 H, J(7,6) = 6.5, J(7′,6) =
6.3, J(6,5) = 5.5 (H-6); 2.82 dd, 1 H, J(4,4′) = 17.0, J(4′,5) = 2.2 (H-4′); 2.90 m br, 1 H (OH);
3.40 d, 1 H, J(2,2′) = 15.6 (H-2); 3.45 d, 1 H, J(2,2′) = 15.6, 1 H (H-2′); 3.62 d br, 2 H,
J(10,10′) = 14.0 (H-10); 3.66 d br, 2 H, J(10,10′) = 14.0 (H-10′); 3.73 s, 3 H (OCH3); 4.25 m ,
1 H (H-5); 7.22–7.32 m , 10 H (H-12, H-13, H-14). 13C NMR: 22.78 (C-9), 23.17 (C-9′), 25.26
(C-8), 35.43 (C-7), 47.87 (C-4), 49.67 (C-2), 52.39 (OCH3), 54.71 (br, C-10), 58.36 (C-6),
67.70 (C-5), 127.02 (C-13), 128.30 (C-12), 129.00 (C-14), 140.00 (C-11), 167.40 (C-1), 203.86
(C-3). MS (70 eV, m/z (rel.%)): 411 (0.1) [M+], 380 (1) [M+ – OCH3], 354 (1) [M+ – C4H9], 266
(100) [C19H24N+], 181 (8), 91 (11) [C7H7+], 65 (3), 42 (3). HRMS C24H30NO3 (M+ – OCH3)
calculated: 380.22257; foun d: 380.22247.
Methyl (5R,6S)-(+)-6-(tert-butyldimethylsilyl)-5-hydroxy-3-oxo-7-phenylheptanoate ((R,S)-10e):
0.76 g (54%) yield from aldeh yde 9e after colum n ch rom atograph y (silica gel, ligh t petro-
leum /dieth yl eth er, 4:1) followin g procedure V; RF 0.27 (ligh t petroleum /dieth yl eth er, 4:1);
[α ]2D0 +45.2 (c 0.93, CH2Cl2); de = 95%, determ in ed by NMR; ee = 93%, determ in ed after
syn-reduction an d acetalisation with 2,2-dim eth oxypropan e by 1H NMR with
(–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ):
3700–3100 (OH), 3084, 3062, 3025, 2955, 2929, 2899, 2883, 2856, 1945, 1870, 1746, 1712
(COOMe), 1654, 1631, 1602, 1495, 1471, 1454, 1438, 1404, 1362, 1325, 1253, 1217, 1148,
1108, 1058, 1009, 825, 810, 700. 1H NMR: 0.07 s, 3 H (H-12); 0.12 s, 3 H (H-12′); 0.96 s, 9 H
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

994
Enders, Burkamp:
(H-14); 1.46 ddd, 1 H, J(6,7) = 9.1, J(6,7′) = 4.4, J(6.5) = 2.5 (H-6); 2.31 dd, 1 H, J(4,4′) =
17.8, J(4,5) = 3.0 (H-4); 2.50 dd, 1 H, J(4,4′) = 17.8, J(4′,5) = 9.3, 1 H (H-4′); 2.76–2.90 m , 2 H
(H-7, H-7′); 3.15 d, 1 H, J(2,2′) = 15.6 (H-2); 3.20 d, 1 H, J(2,2′) = 15.6 (H-2′); 3.66 s, 3 H
(OCH3); 4.35 ddd, 1 H, J(5,4) = 9.3, J(5,4′) = 3.0, J(4,5) = 2.5 (H-5); 7.14–7.32 m , 5 H (H-9,
H-10, H-11). 13C NMR: –5.96 (C-12), –5.81 (C-12′), 17.59 (C-13), 27.29 (C-14), 30.09 (C-6),
31.14 (C-7), 49.38 (C-4), 49.69 (C-2), 52.33 (OCH3), 68.22 (C-5), 125.83 (C-10), 128.41 (C-9),
128.54 (C-11), 143.90 (C-8), 167.26 (C-3), 204.13 (C-1). MS (70 eV, m/z (rel.%)): 364 (0.1)
[M+], 331 (2) [M+ – H2O – CH3], 289 (76) [M+ – H2O – C4H9], 275 (4) [M+ – CH3OH – C4H9],
207 (8), 201 (4), 191 (8), 183 (5), 173 (16), 155 (21), 141 (7), 131 (27), 117 (34), 115 (12)
[TBDMS+], 107 (6), 101 (9), 91 (49) [C7H7+], 75 (100) [C2H7OSi+], 73 (43) [TMS+], 59 (17). For
C
20H32O4Si (364.6) calculated: 65.89% C, 8.85% H; foun d: 65.89% C, 8.60% H.
Methyl (5R,6S)-(+)-6-(tert-butyldimethylsilyl)-7-(2,4-dichlorophenyl)-5-hydroxy-3-oxoheptanoate
((R,S)-10f): 0.65 g (60%) yield from aldeh yde 9f after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 4:1); RF 0.29 (ligh t petroleum /dieth yl eth er, 4:1) followin g
procedure V; [α ]2D0 +47.9 (c 0.61, CH2Cl2); de = 95%, determ in ed by NMR; ee = 95%, deter-
m in ed after syn-reduction an d acetalisation with 2,2-dim eth oxypropan e by 1H NMR with
(–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ):
3650–3300 (OH), 3060, 3040, 2945, 2925, 2895, 2880, 2855, 1950, 1840, 1745, 1710
(COOMe), 1650, 1630, 1585, 1555, 1468, 1440, 1405, 1385, 1320, 1250, 1200, 1155, 1135,
1100, 1050, 1010, 820, 808, 770. 1H NMR: 0.07 s, 3 H (H-14); 0.13 s, 3 H (H-14′); 0.95 s, 9 H
(H-16); 1.54 ddd, 1 H, J(6,7) = 11.3, J(6,7′) = 3.6, J(6,5) = 1.9 (H-6); 2.33 dd, 1 H, J(4,4′) =
12.8, J(4,5) = 4.1 (H-4); 2.39 dd, 1 H, J(4,4′) = 12.8, J(4′,5) = 8.2 (H-4′); 2.65–2.80 s br, 1 H
(OH); 2.80 dd, 1 H, J(7,7′) = 15.1, J(7,6) = 3.6 (H-7); 3.03 dd, 1 H, J(7,7′) = 15.1, J(7′,6) = 11.3
(H-7′); 3.28 s, 2 H (H-2, H-2′); 3.69 s, 3 H (OCH3); 4.33 ddd, 1 H, J(5,4) = 8.2, J(5,4′) = 4.1,
J(6,5) = 1.9 (H-5); 7.18 dd, 1 H, J(12,13) = 8.2, J(12,10) = 2.2 (H-12); 7.28 d, 1 H, J(13,12) =
8.2 (H-13); 7.36 d, 1 H, J(12,10) = 2.2 (H-10). 13C NMR: –5.88 (C-14), –5.78 (C-14′), 17.55
(C-15), 27.23 (C-16), 28.82 (C-6), 28.98 (C-7), 49.48 (C-2, C-4), 52.41 (OCH3), 67.70 (C-5),
127.01 (C-12), 129.39 (C-13), 132.11 (C-10), 132.21 (C-11), 134.52 (C-9), 139.62 (C-8),
167.18 (C-1), 204.09 (C-3). MS (70 eV, m/z (rel.%)): 417 (0.2) [M+ – CH3], 399 (3) [M+ – CH3
–
H2O], 357 (90) [M+ – H2O – C4H9], 343 (5) [M+ – CH3OH – C4H9], 329 (7), 315 (7), 269 (8),
259 (16), 227 (7), 223 (6), 201 (11), 199 (16), 173 (16), 159 (39) [C7H5Cl2+], 129 (5), 115 (8)
[TBDMS+], 101 (12), 93 (17), 89 (31), 75 (100.0) [C2H7SiO+], 59 (23), 43 (39) [C3H7+]. For
C
20H30Cl2O4Si (433.5) calculated: 55.42% C, 6.97% H; foun d: 55.40% C, 6.94% H.
Methyl (5R,6S)-(+)-6-(tert-butylsulfanyl)-5-hydroxy-3-oxo-7-phenylheptanoate ((R,S)-10g): 0.89 g
(87%) yield from aldeh yde 9g after colum n ch rom atograph y (silica gel, ligh t petroleum /di-
eth yl eth er, 4:1) followin g procedure V; RF 0.44 (ligh t petroleum /dieth yl eth er, 2:1); [α ]D20
+52.0 (c 1.21, CH2Cl2); de = 95%, determ in ed by NMR; ee = 93%, determ in ed after syn-redu c-
tion an d acetalisation with 2,2-dim eth oxyp rop an e by 1H NMR with (–)-(R)-1-(9-anthryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3085,
3061, 3028, 2958, 2927, 2899, 2863, 1950, 1870, 1718 (COOMe), 1654, 1631, 1604, 1495,
1439, 1406, 1366, 1325, 1262, 1205, 1162, 1115, 1077, 1031, 933, 860, 810, 753. 1H NMR:
1.18 s, 9 H (H-13); 2.76 dd, 1 H, J(4,4′) = 16.5, J(4,5) = 9.1 (H-4); 2.79–3.01 m , 3 H (H-4′,
H-7, H-7′); 3.02 ddd, 1 H, 1 H, J(6,7) = 8.2, J(6,7′) = 6.3, J(6,5) = 4.4 (H-6); 3.48 s, 2 H (H-2,
H-2′); 3.73 s, 3 H (OCH3); 4.17 m , 1 H (H-5); 7.20–7.32 m , 5 H (H-9, H-10, H-11). 13C NMR:
31.37 (C-13), 39.42 (C-7), 43.86 (C-12), 46.45 (C-4), 49.55 (C-2), 50.81 (C-6), 52.39 (OCH3),
69.23 (C-5), 126.52 (C-10), 128.31 (C-9), 128.56 (C-11), 138.91 (C-8), 167.43 (C-1), 202.22
(C-3). MS (70 eV, m/z (rel.%)): 338 (10.0) [M+], 320 (7.1) [M+ – H2O], 295 (0.7) [M+
–
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New Analogues of Mevinic Acids
995
CH3CO], 264 (2.0), 247 (10.0) [M+ – C7H7], 230 (7), 222 (1.5), 193 (16.5), 173 (57.6), 166
(3.2), 159 (7.8), 145 (19.4) [C6H9O4+], 137 (77), 129 (4.1), 117 (6.0), 113 (12), 104 (10), 101
(12.3), 91 (34.7) [C7H7+], 85 (3.5), 77 (4.7), 71 (4.7), 57 (100) [C4H9+], 43 (21.2) [C3H7+], 41
(22.3) [C3H5+]. For C18H26O4S (338.5) calculated: 63.88% C, 7.74% H; foun d: 64.20% C,
8.01% H.
Methyl (5R,6S)-(+)-6-(tert-butylsulfanyl)-7-(2′,4′-dichlorophenyl)-5-hydroxy-3-oxoheptanoate
((R,S)-10j): 0.92 g (81%) yield from aldeh yde 9j after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 4:1) followin g procedure V; RF 0.13 (ligh t petroleum /dieth yl
eth er, 4:1); [α ]2D0 +45.1 (c 1.25, CH2Cl2); de = 95%, determ in ed by NMR; ee = 94%, deter-
m in ed after syn-reduction an d acetalisation with 2,2-dim eth oxypropan e by 1H NMR with
(–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ):
3700–3200 (OH), 3090, 3063, 3027, 2957, 2899, 2862, 2719, 1747 (COOMe), 1716, 1654,
1632, 1588, 1561, 1495, 1474, 1460, 1439, 1405, 1390, 1366, 1325, 1256, 1203, 1161, 1102,
1078, 1050, 1011, 951, 929, 865, 822, 764, 701, 656. 1H NMR: 1.06 s, 9 H (H-15); 2.60 dd, 1 H,
J(7,7′) = 13.5, J(7,6) = 10.2 (H-7); 2.84–2.96 m , 2 H (H-4, H-4′); 3.05 ddd, 1 H, J(6,7) = 10.2,
J(6,7′) = 4.4, J(6,5) = 3.8 (H-6); 3.15 dd, 1 H, J(7,7′) = 13.5, J(7′,6) = 4.4 (H-7′); 3.55 s br, 2 H
(H-2, H-2′); 3.75 s, 3 H (OCH3); 4.29 m , 1 H (H-5); 7.18 dd, 1 H, J(12,13) = 8.2, J(12,10) =
1.9 (H-12); 7.24 d br, 1 H, J(13,12) = 8.2 (H-13); 7.35 d, 1 H, J(12,10) = 1.9 (H-10). 13C NMR:
31.18 (C-15), 35.30 (C-7), 43.79 (C-14), 46.53 (C-4), 48.11 (C-6). 49.66 (C-2), 52.41 (OCH3),
70.72 (C-5), 126.62 (C-12), 128.98 (C-13), 133.02 (C-11), 134.04 (C-10), 134.75 (C-9), 135.30
(C-8), 167.41 (C-1), 201.95 (C-3). MS (70 eV, m/z (rel.%)): 407 (0.1) [M+], 388 (0.3) [M+
H2O], 371 (18.2) [M+
Cl], 315 (3.9), 297 (12.9), 286 (0.8), 279 (2.9), 261 (4.9)
–
–
[C12H15Cl2S+], 227 (4.3), 205 (18.2), 191 (3.2), 173 (36.9), 159 (15), 145 (21.9) [C6H9O4+],
134 (3), 113 (12), 101 (13.5), 85 (3.7), 75 (8.3), 57 (100) [C4H9+], 43 (22.9) [C3H7+], 41 (25)
[C3H5+]. For C18H24Cl2O4S (407.4) calculated: 53.10% C, 5.94% H; foun d: 53.08% C, 6.17% H.
(+)-6-[(2R,3S)-3-(tert-Butylsulfanyl)-2-hydroxy-4-phenylbutyl]-2,2-dimethyl-4H-1,3-dioxin-4-one
((R,S)-13i): 1.05 g (86%) yield from aldeh yde 9i after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 2:1) followin g procedure VI; RF 0.27 (ligh t petroleum /dieth yl
eth er, 2:1); [α ]2D0 +52.8 (c 0.78, CH2Cl2); de = 92%, determ in ed by NMR; ee = 93%, de-
term in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t
(6 equiv.). IR (KBr): 3500–3200 (OH), 3082, 3062, 3026, 3002, 2974, 2963, 2939, 2899, 2858,
1947, 1865, 1707 (COO), 1636, 1494, 1470, 1455, 1438, 1421, 1392, 1357, 1341, 1326,
1308, 1283, 1256, 1206, 1182, 1152, 1084, 1072, 1057, 1027, 1018, 1006, 967, 935, 908,
879, 862, 840, 810, 708, 701, 638, 627. 1H NMR: 1.21 s, 9 H (H-13); 1.67 s, 3 H (H-15); 1.68 s,
3 H (H-15′); 2.27 dd, 1 H, J(4,4′) = 14.6, J(4,5) = 10.2 (H-4); 2.53 dd, 1 H, J(4,4′) = 14.6,
J(4′,5) = 3.0 (H-4′); 2.58 m , 1 H (OH); 2.86 dd, 1 H, J(7,7′) = 14.0, J(7,6) = 8.0 (H-7); 2.92 dd,
1 H, J(7,7′) = 14.0, J(7′,6) = 7.6 (H-7′); 3.06 ddd, 1 H, J(6,7) = 8.0, J(6,7′) = 7.6, J(6,5) = 3.8
(H-6); 3.95 m , 1 H (H-5); 5.32 s, 1 H (H-2); 7.19–7.36 m , 5 H (H-9, H-10, H-11). 13C NMR:
24.21 (C-15), 25.73 (C-15′), 31.34 (C-13), 37.46 (C-7), 40.31 (C-4), 43.95 (C-12), 51.84 (C-6),
69.20 (C-5), 95.35 (C-2), 106.63 (C-14), 126.71 (C-10), 128.42 (C-9), 129.32 (C-11), 138.54
(C-8), 161.04 (C-1), 169.18 (C-3). MS (70 eV, m/z (rel.%)): 364 (7.9) [M+], 346 (1) [M+
–
H2O], 307 (2.2) [M+ – C4H9], 306 (9.3), 288 (24.3), 273 (0.8), 250 (10.3), 232 (29.9), 217
(5.3), 215 (3.3), 199 (5.9), 197 (2.3), 188 (7.3), 171 (3.7) [M+ – C12H17S], 159 (33.7), 157
(4.5), 147 (4.3), 137 (62.6), 113 (24.3), 104 (11.9), 91 (43.6) [C7H7+], 84 (10.2), 69 (22.3), 59
(46.5), 57 (100) [C4H9+], 43 (23.2), 41 (28.8). For C20H28O4S (364.5) calculated: 65.90% C,
7.74% H; foun d: 66.10% C, 7.85% H.
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996
Enders, Burkamp:
(–)-2,2-Dimethyl-6-[(2R,3S)-2-hydroxy-4-methylpentyl-3-(phenylsulfanyl)]-1,3-4H-dioxin-4-one
((R,S)-13j): 0.94 g (89%) yield from aldeh yde 9j after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 2:1) followin g procedure VI; RF 0.21 (ligh t petroleum /dieth yl
eth er, 2:1); [α ]2D0 –22.5 (c 1.17, CH2Cl2); de = 52%, determ in ed by NMR; ee = 80%, de-
term in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t
(6 equiv.). IR (in CHCl3): 3600–3200 (OH), 3078, 3060, 3015, 2963, 2872, 1950, 1875, 1718
(COO), 1634, 1584, 1480, 1462, 1439, 1392, 1378, 1277, 1258, 1216, 1128, 1088, 1062,
1018, 965, 906, 875, 808, 692, 668. 1H NMR: 1.06 d, 3 H, J(8,7) = 6.6 (H-8); 1.30 d, 3 H,
J(8′,7) = 6.6 (H-8′); 1.66 s br, 6 H (H-14, H-14′); 2.21 m , 1 H (H-7); 2.29 dd, 1 H, J(4,4′) =
14.5, J(4,5) = 9.9 (H-4); 2.70 dd, 1 H, J(4,4′) = 14.5, J(4′,5) = 3.0 (H-4′); 2.87 s br, 1 H (OH);
3.02 dd, 1 H, J(6,7) = 6.3, J(6,5) = 5.5 (H-6); 4.68 m , 1 H (H-5); 5.13 s br, 1 H (H-2);
7.18–7.48 m , 5 H (H-10, H-11, H-12). 13C NMR: 19.11 (C-8), 21.50 (C-8′), 24.46 (C-14),
25.47 (C-14′), 29.34 (C-7), 38.56 (C-4), 64.42 (C-6), 69.75 (C-5), 95.20 (C-2), 106.68 (C-13),
126.88 (C-11), 129.15 (C-10), 131.08 (C-12), 136.38 (C-9), 161.27 (C-1), 169.57 (C-3). MS
(70 eV, m/z (rel.%)): 336 (18) [M+], 278 (38.8) [M+ – C3H6O], 260 (31.7), 218 (1.9), 194
(12.4), 191 (15.3), 169 (6.1), 167 (12.1), 166 (74.2), 165 (100) [C10H13S+], 151 (94.6), 135
(4.5), 123 (50.3), 113 (59.4), 110 (25.6), 109 (19.5), 91 (4.8) [C7H7+], 87 (13.6), 85 (10.7), 69
(43.3), 65 (10), 57 (14.5), 55 (47.6), 45 (14.1), 43 (32.7) [C3H7+], 41 (20.5). For C18H24O4S
(336.5) calculated: 64.26% C, 7.19% H; foun d: 64.15% C, 7.34% H.
Methyl (3S,5R,6S)-(–)-6-(dibenzylamino)-3,5-dihydroxy-7-methyloctanoate ((S,R,S)-11a): 0.56 g
(67%) yield from oxoester 10a after colum n ch rom atograph y (silica gel, ligh t petroleum /di-
eth yl eth er, 4:1) followin g procedure VII; RF 0.30 (ligh t petroleum /dieth yl eth er, 1:1); m .p.
78 °C; [α ]2D0 –9.1 (c 0.63, CH2Cl2); de > 96%, determ in ed by NMR; ee > 96%, determ in ed after
acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-tri-
fluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3100 (OH), 3085, 3062, 3023,
2954, 2872, 2801, 1950, 1883, 1825, 1728 (COOMe), 1602, 1562, 1494, 1453, 1439, 1403,
1363, 1270, 1217, 1160, 1095, 1070, 1028, 992, 969, 701. 1H NMR: 0.94 d, 3 H, J(8,7) = 6.6
(H-8); 1.24 d, 3 H, J(8′,7) = 6.6 (H-8′); 1.56 ddd, 1 H, J(4,4′) = 14.0, J(4,3) = 11.0, J(4,5) = 9.3
(H-4); 1.76 ddd, 1 H, J(4,4′) = 14.0, J(4′,3) = 2.2, J(4′,5) = 1.6 (H-4′); 2.17 m , 1 H (H-7);
2.43 dd, 1 H, J(2,2′) = 15.8, J(2,3) = 5.5 (H-2); 2.51 dd, 1 H, J(6,7) = 9.3, J(6,5) = 5.5 (H-6);
2.53 dd, 1 H, J(2,2′) = 15.8, J(2′,3) 7.4 (H-2′); 3.67 s, 3 H (OCH3); 3.74 d, 2 H, J(9,9′) = 13.5
(H-9); 3.87 d br, 2 H, J(9,9′) = 13.5 (H-9′); 4.20 m , 1 H (H-5), 4.26 m , 1 H (H-3); 7.22–7.36 m ,
10 H (H-11, H-12, H-13). 13C NMR: 20.68 (C-8), 23.18 (C-8′), 28.01 (C-7), 38.35 (C-4), 41.70
(C-2), 51.66 (OCH3), 56.15 (C-9), 66.82 (C-6), 69.67 (C-3), 70.95 (C-5), 127.38 (C-12), 128.56
(C-10), 129.16 (C-13), 139.54 (C-10), 172.43 (C-1). MS (70 eV, m/z (rel.%)): 399 (0.2) [M+],
356 (1) [M+ – C3H7], 252 (35) [C6H11O4+], 181 (6), 160 (3), 91 (100) [C7H7+], 84 (4), 65 (6),
43 (2), 41 (3). For C24H33NO4 (399.5) calculated: 72.15% C, 8.32% H, 3.50% N; foun d:
72.15% C, 8.46% H, 3.77% N.
Methyl (3S,5R,6S)-(–)-6-(dibenzylamino)-3,5-dihydroxy-7,7-dimethyloctanoate ((S,R,S)-11b ):
0.48 g (51%) yield from oxoester 10b after colum n ch rom atograph y (silica gel, ligh t petro-
leum /dieth yl eth er, 4:1) followin g procedure VII; RF 0.38 (ligh t petroleum /dieth yl eth er,
1:1); m .p. 86 °C; [α ]2D0 –20.2 (c 1.4, CH2Cl2); de > 96%, determ in ed by NMR; ee > 96%, deter-
m in ed after acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3100 (OH), 3085,
3063, 3024, 2954, 2872, 2799, 1950, 1880, 1810, 1728 (COOMe), 1602, 1494, 1453, 1439,
1358, 1271, 1174, 1094, 1074, 1028, 992, 758, 700. 1H NMR: 1.06 s, 9 H (H-8); 1.64 ddd, 1 H,
J(4,4′) = 14.3, J(4,3) = 2.2, J(4,5) = 2.1 (H-4); 1.84 ddd, 1 H, J(4,4′) = 14.3, J(4′,3) = 10.4,
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New Analogues of Mevinic Acids
997
J(4′,5) = 10.2 (H-4′); 2.41–2.49 m , 3 H (H-6, H-2, H-2′); 3.28–3.34 m br, 2 H (H-9); 3.72 s, 3 H
(OCH3); 3.81–4.11 m br, 2 H (H-9′); 4.16 m , 1 H (H-5); 4.21 m , 1 H (H-3); 7.20–7.36 m , 10 H
(H-11, H-12, H-13). 13C NMR: 29.89 (C-8), 37.36 (C-7), 41.48 (C-4), 43.12 (C-2), 51.82
(OCH3), 56.78 (br, C-9), 69.10 (C-6), 69.95 (C-3), 72.65 (C-5), 126.90 (C-12), 128.19 (C-11),
129.26 (br, C-13), 140.17 (br, C-10), 172.92 (C-1). MS (70 eV, m/z (rel.%)): 412 (0.1) [M+ – 1],
382 (1) [M+ – OCH3], 356 (20) [M+ – C(CH3)3], 266 (36) [C19H24N+], 181 (9), 162 (2), 106 (3),
91 (100) [C7H7+], 65 (6), 57 (4), 43 (4), 41 (4). For C25H35NO4 (413.6) calculated: 72.61% C,
8.53% H, 3.39% N; foun d: 72.71% C, 8.15% H, 3.61% N. HRMS C21H26NO4 (M+ – C4H9) cal-
culated: 356.1862; foun d: 356.1862.
Methyl (3S,5R,6S)-(+)-6-(dibenzylamino)-3,5-dihydroxy-7-phenylheptanoate ((S,R,S)-11c): 0.61 g
(61%) yield from oxoester 10c after colum n ch rom atograph y (silica gel, ligh t petroleum /di-
eth yl eth er, 4:1) followin g procedure VII; RF 0.15 (ligh t petroleum /dieth yl eth er, 2:1); [α ]D20
+11.6 (c 0.9, CH2Cl2); de > 96%, determ in ed by NMR; ee > 96%, determ in ed after
acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-tri-
fluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3085, 3062, 3026,
2951, 2843, 2803, 1950, 1877, 1810, 1734 (COOMe), 1602, 1585, 1495, 1453, 1439, 1365,
1309, 1255, 1217, 1170, 1104, 1073, 1051, 1029, 992, 973, 700. 1H NMR: 1.47 ddd, 1 H,
J(4,4′) = 14.0, J(4,3) = 10.4, J(4,5) = 10.2 (H-4); 1.82 dt, 1 H, J(4,4′) = 14.0, J(4′,3) = J(4′,5) =
2.2 (H-4′); 2.41 dd, 1 H, J(2,2′) = 16.2, J(2,3) = 5.2 (H-2); 2.47 dd, 1 H, J(2,2′) = 16.2, J(2′,3) =
7.4 (H-2′); 2.86 dd, 1 H, J(7,7′) = 13.5, J(7,6) = 6.3 (H-7); 2.98 ddd, 1 H, J(6,7′) = 6.9, J(6,7) =
6.3, J(6,5) = 4.9 (H-6); 3.09 dd, 1 H, J(7,7′) = 13.5, J(7′,6) = 6.9 (H-7′); 3.61 d br, 2 H, J(12,12′) =
13.7 (H-12); 3.69 s, 3 H (OCH3); 3.77 d br, 2 H, J(12,12′) = 13.7 (H-12′); 3.95 ddd, 1 H, J(5,4) =
10.2, J(5,6) = 4.9, J(5,4′) = 2.2 (H-5); 4.16 dddd, 1 H, J(3,4) = 10.4, J(3,2′) = 7.4, J(3,2) = 5.2,
J(3,4′) = 2.2 (H-3); 7.16–7.35 m , 15 H (H-9, H-10, H-11, H-14, H-15, H-16). 13C NMR: 31.89
(C-7), 39.64 (C-4), 41.56 (C-2), 51.77 (OCH3), 55.06 (C-12), 63.54 (C-6), 69.34 (C-3), 72.05
(C-5), 126.05 (C-11), 127.05 (C-16), 128.32 (C-10), 128.40 (C-15), 128.80 (C-12), 129.38
(C-17), 139.61 (C-9), 140.40 (C-14), 172.68 (C-1). MS (70 eV, m/z (rel.%)): 446 (0.2) [M+ – 1],
416 (3) [M+ – OCH3], 356 (22) [M+ – C7H7], 300 (100) [C22H22N+], 265 (2), 208 (2), 181 (8),
132 (2), 91 (90) [C7H7+], 65 (4), 45 (3). For C28H33NO4 (447.6) calculated: 75.14% C,
7.43% H, 3.13% N; foun d: 75.52% C, 7.17% H, 3.61% N. HRMS C27H30NO3 (M+ – OCH3)
calculated: 416.2226; foun d: 416.2225.
Methyl (3S,5R,6S)-(+)-6-(tert-butyldimethylsilyl)-3,5-dihydroxy-7-phenylheptanoate ((S,R,S)-11e):
0.46 g (55%) yield from oxoester 10e after colum n ch rom atograph y (silica gel, ligh t petro-
leum /dieth yl eth er, 4:1) followin g procedure VII; RF 0.19 (ligh t petroleum /dieth yl eth er,
2:1); [α ]2D0 +32.7 (c 0.6, CH2Cl2); de >96%, determ in ed by NMR; ee = 93%, determ in ed after
acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-tri-
fluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3083, 3061, 3025,
3001, 2954, 2929, 2883, 2856, 1950, 1870, 1737 (COOMe), 1602, 1495, 1454, 1438, 1363,
1252, 1221, 1162, 1091, 1030, 837, 825, 810, 767, 701. 1H NMR: 0.06 s, 3 H (H-12); 0.15 s, 3 H
(H-12′); 0.96 s, 9 H (H-14); 1.32 dt, 1 H, J(4,4′) = 14.3, J(4,5) = J(4,3) = 2.5 (H-4); 1.48 ddd, 1 H,
J(6,7) = 10.2, J(6,7′) = 3.6, J(6,5) = 2.8 (H-6); 1.53 dt, 1 H, J(4,4′) = 14.3, J(4′,3) = J(4′,5) = 10.2
(H-4′); 2.25 dd, 1 H, J(2,2′) = 16.5, J(2,3) = 4.4 (H-2); 2.33 dd, 1 H, J(2.2′) = 16.5, J(2′,3) = 7.7
(H-2′); 2.73 dd, 1 H, J(7,7′) = 15.4, J(7,6) = 10.2 (H-7); 2.86 dd, 1 H, J(7,7′) = 15.4, J(7′,6) = 3.6
(H-7′); 3.00–3.50 s br, 2 H (OH); 3.66 s, 3 H (OCH3); 4.03 dddd, 1 H, J(3,4′) = 10.2, J(3,2′) =
7.7, J(3,2) = 4.4, J(3,4) = 2.5 (H-3); 4.09 ddd, 1 H, J(6,4′) = 10.2, J(6,5) = 2.8, J(6,4) = 2.5
(H-6); 7.11–7.28 m , 5 H (H-9, H-10, H-11). 13C NMR: –5.74 (C-12), –5.30 (C-12′), 17.61
(C-13), 27.32 (C-14), 31.70 (C-6), 32.00 (C-7), 41.39 (C-4), 41.66 (C-2), 51.74 (OCH3), 69.37
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

998
Enders, Burkamp:
(C-3), 73.33 (C-5), 125.64 (C-11), 128.31 (C-10), 128.43 (C-12), 143.73 (C-9), 172.95 (C-1).
MS (70 eV, m/z (rel.%)): 333 (1) [M+ – H2O – CH3], 317 (1) [M+ – H2O – CH3O], 291 (43) [M+
– H2O – C4H9], 277 (3) [M+ – CH3OH – C4H9], 259 (6) [277+ – H2O], 185 (21) [291+ – C8H10],
167 (8), 157 (18), 143 (100), 129 (17), 117 (21) [C5H9O3+], 115 (10) [TBDMS+], 107 (5), 91 (50)
[C7H7+], 89 (9), 75 (68) [C2H7OSi+], 73 (31), 71 (8), 59 (9), 57 (5) [C4H9+]. For C20H34O4Si
(366.6) calculated: 65.53% C, 9.35% H; foun d: 65.83% C, 9.64% H.
Methyl (3S,5R,6S)-(+)-6-(tert-butyldimethylsilyl)-3,5-dihydroxy-7-(2,4-dichlorophenyl)heptanoate
((S,R,S)-11f): 0.41 g (52%) yield from oxoester 10f after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 4:1) followin g procedure VII; RF 0.12 (ligh t petroleum /dieth yl
eth er, 2:1); [α ]2D0 +30.7 (c 0.6, CH2Cl2); de > 96%, determ in ed by NMR; ee = 95%, determ in ed
after acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3060,
3016, 2955, 2929, 2883, 2857, 2000, 1900, 1728 (COOMe), 1586, 1559, 1472, 1439, 1386,
1363, 1340, 1312, 1255, 1215, 1202, 1169, 1137, 1101, 1050, 1008, 935, 865, 825, 810, 759,
715, 702. 1H NMR: 0.06 s, 3 H (H-14); 0.13 s, 3 H (H-14′); 0.96 s, 9 H (H-16); 1.32 ddd, 1 H,
J(4,4′) = 14.3, J(4,3) = 2.7, J(4,5) = 2.2 (H-4); 1.42 ddd, 1 H, J(4,4′) = 14.3, J(4′,3) = 10.1,
J(4′,5) = 9.6 (H-4′); 1.59 ddd, 1 H, J(6,7) = 11.3, J(6,7′) = 3.6, J(6,5) = 2.5 (H-6); 2.34 d, 2 H,
J(2,3) = J(2′,3) = 6.0 (H-2, H-2′); 2.79 dd, 1 H, J(7,7′) = 15.1, J(7,6) = 3.6 (H-7); 2.96 dd, 1 H,
J(7,7′) = 15.1, J(7′,6) = 11.3 (H-7′); 3.20 - 3.50 s br, 2 H (OH, OH′); 3.68 s, 3 H (CO2CH3);
4.03 ddd, 1 H, J(5,4′) = 9.6, J(5,6) = 2.5, J(5,4) = 2.2 (H-5); 4.07 ddt, 1 H, J(3,4′) = 10.1, J(3,4) =
2.7, J(3,2) = J(3,2′) = 6.0 (H-3); 7.16 dd, 1 H, J(12,13) = 8.2, J(12,10) = 2.2 (H-12); 7.26 d, 1 H,
J(12,13) = 8.2 (H-13); 7.33 d, 1 H, J(10,12) = 2.2 (H-10). 13C NMR: –5.71 (C-14), –5.29
(C-14′), 17.60 (C-15), 27.29 (C-18), 29.46 (C-7), 30.35 (C-6), 41.32 (C-4), 41.55 (C-2), 51.81
(OCH3), 69.68 (C-3), 73.10 (C-5), 126.90 (C-12), 129.21 (C-13), 131.87 (C-10), 131.98 (C-11),
134.52 (C-9), 139.60 (C-8), 172.97 (C-1). MS (70 eV, m/z (rel.%)): 401 (0.9) [M+ – CH3
–
H2O], 385 (2) [M+ – H2O – CH3O], 359 (56) [M+ – H2O – C4H9], 327 (7), 285 (3), 253 (12),
225 (17), 211 (61), 197 (8), 185 (8), 176 (9), 161 (35), 159 (58), 149 (6), 141 (5), 129 (5), 119
(11), 115 (10) [TBDMS+], 107 (10), 105 (13),1 01 (4), 91 (10), 89 (24), 75 (100) [C2H7OSi+],
73 (52) [TMS+], 71 (17), 59 (14), 57 (15) [C4H9+], 55 (13), 45 (16), 43 (60), 41 (14). For
C
20H32Cl2O4Si (435.5) calculated: 55.16% C, 7.41% H; foun d: 54.90% C, 7.51% H.
Methyl (3S,5R,6S)-(+)-6-(tert-butylsulfanyl)-3,5-dihydroxy-7-phenylheptanoate ((S,R,S)-11i):
0.51 g (78%) yield from oxoester 10i after colum n ch rom atograph y (silica gel, ligh t petro-
leum /dieth yl eth er, 4:1) followin g procedure VII; RF 0.14 (ligh t petroleum /dieth yl eth er,
2:1); m .p. 75–76 °C; 35.0 (c 0.6, CH2Cl2); de = 80%, determ in ed by NMR; ee = 93%, deter-
m in ed after acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3100 (OH), 3080,
3061, 3031, 2968, 2955, 2862, 1737 (COOMe), 2686, 1677, 1655, 1648, 1637, 1618, 1603,
1561, 1523, 1509, 1498, 1445, 1377, 1366, 1335, 1294, 1245, 1202, 1164, 1108, 1072, 1049,
1031, 1005, 935, 858, 750, 705. 1H NMR: 1.19 s, 9 H (H-13); 1.65 ddd, 1 H, J(4,4′) = 14.1,
J(4,5) = 10.4, J(4,3) = 9.1 (H-4); 1.83 ddd, 1 H, J(4,4′) = 14.1, J(4′,3) = 3.3, J(4′,5) = 2.4 (H-4′);
2.47 dd, 1 H, J(2,2′) = 16.2, J(2,3) = 5.2 (H-2); 2.54 dd, 1 H, J(2,2′) = 16.2, J(2′,3) = 7.4 (H-2′);
2.82–3.01 m , 3 H (H-6, H-7, H-7′); 3.14 s br, 1 H (OH); 3.71 s, 3 H (OCH3); 3.88 s br, 2 H
(OH′, H-5); 4.24 dddd, 1 H, J(3,4) = 9.1, J(3,2′) = 7.4, J(3,2) = 5.2, J(3,4′) = 3.3 (H-3);
7.19–7.32 m , 5 H (H-9, H-10, H-11). 13C NMR: 31.38 (C-13), 38.30 (C-7), 39.56 (C-4), 41.45
(C-2), 43.64 (C-12), 51.75 (OCH3), 51.88 (C-6), 68.41 (C-3), 72.72 (C-5), 126.44 (C-10),
130.07 (C-9), 135.68 (C-11), 143.73 (C-8), 172.56 (C-1). MS (70 eV, m/z (rel.%)): 340 (1)
[M+], 323 (2) [M+ – H2O], 322 (1) [M+ – H2O], 291 (2) [M+ – CH3O – H2O], 235 (3) [291+
–
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
999
C4H8], 219 (5) [M+ – CH3OH – SC4H9], 201 (54) [219+ – H2O], 194 (31) [250+ – C4H8], 193
(8) [M+ – C6H11O4], 175 (16), 159 (25) [201+ – H2C=C=O], 147 (14) [C6H11O4+], 138 (27)
[194+ – C4H8], 137 (44) [194+ – C4H9], 129 (47) [147+ – H2O], 115 (9) [147+ – CH3OH], 103
(16) [194+ – C7H7], 97 (22) [C5H5O2+], 91 (50) [C7H7+], 73 (23), 57 (100) [C4H9+], 43 (10)
[C3H7+], 41 (17) [C3H5+]. For C18H28O4S (340.5) calculated: 63.50% C, 8.29% H; foun d:
63.53% C, 8.27% H.
Methyl (3S,5R,6S)-(+)-6-(tert-butylsulfanyl)-7-(2,4-dichlorophenyl)-3,5-dihydroxyheptanoate
((S,R,S)-11j): 0.73 g (86%) yield from oxoester 10j after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 4:1) followin g procedure VII; RF 0.18 (ligh t petroleum /dieth yl
eth er, 2:1); [α ]2D0 +9.4 (c = 0.6, CH2Cl2); de = 80%, determ in ed by NMR; ee = 94%, deter-
m in ed after acetalisation with 2,2-dim eth oxypropan e by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3700–3200 (OH), 3080,
3060, 3006, 2963, 2935, 2872, 1950, 1870, 1718 (COOMe), 1634, 1584, 1480, 1439, 1392,
1378, 1277, 1258, 1215, 1205, 1128, 1058, 1063, 1018, 965, 906, 875, 839, 808, 692. 1H NMR:
1.07 s, 9 H (H-15); 1.78 ddd, 1 H, J(4,4′) = 14.3, J(4,5) = 9.6, J(4,3) = 9.1 (H-4); 1.85 ddd, 1 H,
J(4,4′) = 14.3, J(4′,3) = 3.3, J(4′,5) = 3.0 (H-4′); 2.51 dd, 1 H, J(2,2′) = 15.9, J(2,3) = 4.9 (H-2);
2.59 dd, 1 H, J(2,2′) = 15.9, J(2′,3) = 7.4 (H-2′); 2,66 dd, 1 H, J(7,7′) = 13.5, J(7,6) = 10.4
(H-7); 3.01 ddd, 1 H, J(6,7) = 10.4, J(6,7′) = 4.7, J(6,5) = 3.3 (H-6); 3.15 dd, 1 H, J(7,7′) =
13.5, J(7′,6) = 4.7 (H-7′); 3.32 s br, 1 H (OH); 3.90 s br, 1 H (OH′); 4.02 ddd, 1 H, J(5,4) = 9.6,
J(5,6) = 3.3, J(5,4′) = 3.0 (H-5); 4.30 dddd, 1 H, J(3,4) = 9.1, J(3,2′) = 7.4, J(3,2) = 4.9, J(3,4′) =
3.3 (H-3); 7.17 dd, 1 H, J(12,13) = 8.2, J(12,10) = 1.9 (H-12); 7.23 d br, 1 H, J(13,12) = 8.2
(H-13); 7.35 d, 1 H, J(10,12) = 1.9 (H-10). 13C NMR: 31.19 (C-15), 35.35 (C-7), 38.81 (C-4),
41.53 (C-2), 43.55 (C-14), 48.94 (C-6), 51.76 (OCH3), 68.43 (C-3), 74.59 (C-5), 126.52 (C-12),
128.97 (C-13), 132.92 (C-11), 134.03 (C-10), 134.73 (C-9), 135.53 (C-8), 172.60 (C-1). MS (70 eV,
m/z (rel.%)): 408 (0.2) [M+], 373 (11) [M+ – Cl], 341 (1) [373+ – CH3OH], 317 (1) [373+
C4H8], 299 (5) [317+ – H2O], 285 (4) [341+ – C4H8], 261 (3) [M+ – C6H11O4], 227 (17) [261+
–
–
H2S], 205 (10) [261+ – C4H8], 171 (10), 159 (14) [C7H5Cl2+], 147 (13) [C6H11O4+], 143 (6),
129 (46) [147+ – H2O], 115 (5) [147+ – CH3OH], 103 (8), 97 (25) [C5H5O2+], 71 (8), 57 (100)
[C4H9+], 43 (16) [C3H7+], 41 (28). HRMS C18H26ClO4S (M+ – Cl) calculated: 373.1240; foun d:
373.1239.
(6R)-(–)-6-[(1S)-(Dibenzylamino)-3-methylbutyl]-4-hydroxy-5,6-dihydropyran-2-one ((S,R)-14d ):
0.54 g (76%) yield from δ-h ydroxy-β-ketoester 10d after colum n ch rom atograph y (silica gel,
ligh t petroleum /dieth yl eth er, 1:2) followin g procedure VIII; RF 0.23 (ligh t petroleum /dieth yl
eth er, 1:2); [α ]2D0 –21.7 (c 0.45, CH2Cl2); m .p. 80 °C (dec.); de = 95%, determ in ed by NMR;
ee > 96%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as
ch iral cosolven t (6 equiv.). IR (KBr): 3700–2400, 3084, 3061, 3026, 2951, 2867, 2843, 2817,
2744, 2693, 2637, 2582, 1958, 1871, 1814, 1750 (CO), 1719 (COO), 1646, 1613, 1584, 1494,
1481, 1467, 1455, 1413, 1400, 1382, 1367, 1354, 1295, 1248, 1230, 1195, 1170, 1120, 1045,
1038, 982, 957, 925, 882, 828, 755, 735, 702. 1H NMR: 0.75 d, 3 H, J(9,8) = 6.6 (H-9); 0.94 d,
3 H, J(9′,8) = 6.6 (H-9′); 1.34 ddd, 1 H, J(7,7′) = 13.5, J(7,8) = 8.5, J(7,6) = 5.2 (H-7); 1.84 m ,
1 H (H-7′); 1.97 m , 1 H (H-8); 2.34 dd, 1 H, J(4,4′) = 18.7, J(4,5) = 11.5 (H-4); 2.73 m , 1 H
(H-6); 3.53 d br, 1 H, J(4,4′) = 18.7 (H-4′); 3.60 d br, 2 H, J(10,10′) = 14.0 (H-10); 3.78 d br,
2 H, J(10,10′) = 14.0 (H-10′); 4.62 s br, 1 H (H-2); 4.75 ddd, 1 H, J(5,4) = 11.5, J(5,6) = 5.0,
J(5,4) = 2.7 (H-5); 7.21–7.35 m , 10 H (H-12, H-13, H-14). 13C NMR: 23.00 (C-9), 23.90 (C-9′),
25.76 (C-8), 36.32 (C-7), 42.83 (C-4), 47.72 (C-2), 55.11 (C-10), 58.13 (C-6), 76.46 (C-5),
127.92 (C-13), 129.06 (C-12), 129.51 (C-14), 139.73 (C-11), 167.76 (C-1), 200.90 (C-3). MS
(70 eV, m/z (rel.%)): 379 (0.1) [M+], 278 [M+ – 101], 266 (20) [M+ – C5H5O3+], 181 (2), 118
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

1000
Enders, Burkamp:
(1), 91 (100) [C7H7+], 77 (1), 65 (8), 44 (7). For C24H29NO3 (379.5) calculated: 75.96% C,
6.90% H, 3.69% N; foun d: 75.63% C, 6.78% H, 3.89% N.
(6R)-(–)-6-[(1S)-(Dibenzylamino)-3-methylbutyl]-4-methoxy-5,6-dihydropyran-2-one ((S,R)-15d ):
0.64 g (86%) yield from 4-oxo-5,6-dih ydropyran e 14d after colum n ch rom atograph y (silica
gel, ligh t petroleum /dieth yl eth er, 1:2) followin g procedure VIII; RF 0.39 (ligh t petroleum /di-
eth yl eth er, 1:2); [α ]2D0 –8.2 (c 0.56, CH2Cl2); m .p. 92 °C; de = 95%, determ in ed by NMR; ee >
96%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral
cosolven t (6 equiv.). IR (KBr): 3105, 3084, 3062, 3028, 2928, 2924, 2866, 2813, 1713, 1635,
1545, 1494, 1468, 1455, 1384, 1343, 1319, 1292, 1252, 1227, 1200, 1181, 1120, 1081, 1068,
1039, 999, 973, 955, 835, 753, 733, 702, 676, 663. 1H NMR: 0.72 d, 3 H, J(9,9′) = 6.4 (H-9);
0.92 d, 3 H, J(9′,8) = 6.7 (H-9′); 1.34 ddd, 1 H, J(7,7′) = 14.3, J(7,8) = 7.9, J(7,6) = 5.2 (H-7);
1.77 ddd, 1 H, J(7,7′) = 14.3, J(7′,6) = 7.6, J(7′,8) = 5.8 (H-7′); 1.96 m , 1 H (H-8); 2.35 dd, 1 H,
J(4,4′) = 17.1, J(4,5) = 4.3 (H-4); 2.46 ddd, 1 H, J(4,4′) = 17.1, J(4′,5) = 11.5, J(4′,2) = 1.5
(H-4′), 2.75 dt, 1 H, J(6,7′) = 7.6, J(6,5) = J(6,7) = 5.2 (H-6); 3.57 d br, 2 H, J(10,10′) = 13.7
(H-10); 3.69 s, 3 H (OCH3); 3.77 d br, 2 H, J(10,10′) = 14.0 (H-10′); 4.64 ddd, 1 H, J(5,4′) =
11.5, J(5,6) = 5.2, J(5,4) = 4.3 (H-5); 5.09 d, 1 H, J(2,4′) = 1.5 (H-2); 7.21–7.32 m , 10 H (H-12,
H-13, H-14). 13C NMR: 22.39 (C-9), 23.41 (C-9′), 25.06 (C-8), 31.40 (C-4), 35.86 (C-7), 54.32
(C-10), 55.90 (OCH3), 57.16 (C-6), 75.74 (C-5), 90.15 (C-2), 127.21 (C-13), 128.28 (C-12),
128.94 (C-14), 139.66 (C-11), 167.21 (C-3), 172.98 (C-1). MS (70 eV, m/z (rel.%)): 266 (44)
[C19H24N+], 181 (6), 174 (3), 92 (7), 91 (100) [C7H7+], 65 (7), 42 (9). For C25H31NO3 (393.5)
calculated: 76.30% C, 7.94% H, 3.56% N; foun d: 76.51% C, 8.32% H, 3.57% N.
(6R)-(+)-6-[(1S)-(tert-Butylsulfanyl)-2-phenylethyl]-4-methoxy-5,6-dihydropyran-2-one ((S,R)-16i):
1,3-d ioxin e 13i (0.29 g, 0.8 m m ol) was d issolved in m eth an ol (5 m l) an d p otassiu m
carbon ate (0.22 g, 1.6 m m ol) was added at room tem perature wh ile stirrin g. After stirrin g for
12 h th e reaction m ixture was subsequen tly n eutralised with 1 M aqueous h ydroch loric acid.
Stan dard aqueous work-up with dieth yl eth er (30 m l/m m ol) an d water (3 m l/m m ol) resulted in
th e ketoester 10i wh ich was subsequen tly subm itted to procedure VIII to yield 0.22 g (85%)
of a colourless solid after colum n ch rom atograph y (silica gel, ligh t petroleum /dieth yl eth er,
1:1); RF 0.22 (ligh t petroleum /dieth yl eth er, 1:1); [α ]2D0 +51.4 (c 0.65, CH2Cl2); m .p. 114–116 °C;
de = 93%, determ in ed by NMR; ee = 93%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (CHCl3): 3086, 3060, 3014, 2960,
2941,2926, 2900, 2860, 1713, 1625, 1603, 1495, 1457, 1444, 1418, 1388, 1366, 1357, 1292,
1238, 1219, 1162, 1055, 994, 959, 890, 825, 703, 667. 1H NMR: 1.15 s, 9 H (H-13); 2.49 dd,
1 H, J(4,4′) = 17.0, J(4,5) = 3.9 (H-4); 2.70 ddd, 1 H, J(4,4′) = 17.0, J(4′,5) = 12.1, J(4′,2) = 1.7
(H-4′); 2.94 m , 2 H (H-7, H-7′); 3.06 dt, 1 H, J(6,7) = J(6,7′) = 7.2, J(6,5) = 6.4 (H-6); 3.65 s, 3 H
(OCH3); 4.23 ddd, 1 H, J(5,4′) = 12.1, J(5,6) = 6.4, J(5,4) = 3.9 (H-5); 5.05 d, 1 H, J(2,4′) = 1.7
(H-2); 7.10–7.23 m , 5 H (H-9, H-10, H-11). 13C NMR: 30.68 (C-7), 32.02 (C-13), 40.05 (C-4),
44.75 (C-6), 47.94 (C-6), 56.64 (OCH3), 78.05 (C-5), 90.74 (C-2), 127.28 (C-10), 128.84 (C-9),
130.58 (C-11), 138.60 (C-8), 167.50 (C-1), 173.67 (C-3). MS (70 eV, m/z (rel.%)): 320 (5)
[M+], 263 (8) [M+ – C4H9], 231 (4) [M+ – SC4H9], 194 (11) [M+ – C12H18S+], 193 (15) [M+
–
C6H7O3+], 173 (12), 137 (28), 127 (100) [C6H7O3+], 115 (10), 91 (35) [C7H7+], 57 (62), 43
(23), 41 (35). For C25H31NO3 (393.5) calculated: 76.30% C, 7.94% H, 3.56% N; foun d:
76.51% C, 8.32% H, 3.57% N.
Methyl (4S,6R)-(–)-6-[(1S)-(dibenzylamino)-2-methylpropyl]-2,2-dimethyl-1,3-dioxane-4-acetate
((S,S,R)-17a): 0.32 g (55%) yield from dih ydroxyester 11a after colum n ch rom atograph y (sil-
ica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF 0.70 (ligh t petro-
leum /dieth yl eth er, 4:1); [α ]2D0 –40.6 (c 0.9, CH2Cl2); de > 96%, determ in ed by NMR; ee =
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

New Analogues of Mevinic Acids
1001
95%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral
cosolven t (6 equiv.). IR (film ): 3064, 3062, 3024, 2994, 2975, 2947, 2898, 2837, 2814, 1953,
1870, 1742 (COOMe), 1601, 1494, 1453, 1442, 1383, 1355, 1287, 1238, 1204, 1168, 1131,
1110, 1093, 1071, 1051, 1017, 981, 966, 950, 919, 906, 887, 866, 850, 810, 755, 740, 700.
1H NMR: 1.00 d, 3 H, J(8,7) = 6.9 (H-8); 1.10 d, 3 H, J(8′,7) = 6.9 (H-8′); 1.20 ddd, 1 H, J(4,4′) =
12.9, J(4,5) = 11.8, J(4,3) = 11.5 (H-4); 1.32 s, 3 H (H-10); 1.49 s, 3 H (H-10′); 1.76 dt, 1 H,
J(4,4′) = 12.9, J(4′,5) = J(4′,3) = 2.5 (H-4′); 2.20 m , 1 H (H-7); 2.29 dd, 1 H, J(6,7) = 6.3, J(6,5) =
4.4 (H-6); 2.39 dd, 1 H, J(2,2′) = 15.4, J(2,3) = 6.0 (H-2); 2.53 dd, 1 H, J(2,2′) = 15.4, J(2′,3) =
7.1 (H-2′); 3.61 d br, 2 H, J(11,11′) = 13.7 (H-11); 3.67 d br, 2 H, J(11,11′) = 13.7 (H-11′);
3.71 s, 3 H (OCH3); 4.28 m , 1 H (H-5); 4.33 m , 1 H (H-3); 7.21–7.35 m , 10 H (H-13, H-14,
H-15). 13C NMR: 19.32 (C-10), 20.01 (C-8), 23.15 (C-8′), 25.59 (C-7), 30.03 (C-10′), 35.84
(C-4), 41.45 (C-2), 51.61 (OCH3), 54.78 (C-11), 65.19 (C-6), 66.49 (C-3), 67.27 (C-5), 98.56
(C-9), 126.83 (C-14), 128.14 (C-13), 128.96 (C-15), 140.05 (C-12), 171.50 (C-1). MS (70 eV,
m/z (rel.%)): 439 (0.5) [M+], 424 (5) [M+ – CH3], 396 (6) [M+ – CH3CO], 338 (3), 308 (2), 252
(100) [C18H22N+], 210 (5), 181 (7), 160 (3), 91 (61) [C7H7+], 65 (5), 55 (6), 43 (12) [C3H7+].
HRMS C18H24O3S (M+) calculated: 320.14462; foun d: 320.14429.
Methyl (4S,6R)-(–)-6-[(1S)-(dibenzylamino)-2,2-dimethylpropyl]-2,2-dimethyl-1,3-dioxane-4-acetate
((S,S,R)-17b): 0.49 g (68%) yield from dih ydroxyester 11b after colum n ch rom atograph y
(silica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF 0.54 (ligh t petroleum /
dieth yl eth er, 4:1); [α ]2D0 –43.4 (c 0.8, CH2Cl2); de > 96%, determ in ed by NMR; ee > 95%, de-
term in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral cosolven t
(6 equiv.). IR (film ): 3085, 3062, 3025, 2990, 2952, 2871, 2798,1945, 1871, 1800, 1740
(COOMe), 1602, 1585, 1543, 1494, 1454, 1438, 1396, 1381, 1363, 1315, 1262, 1201, 1166,
1121, 1099, 1076, 1028, 1001, 947, 933, 796, 700. 1H NMR: 0.99 s, 9 H (H-8); 1.36 s, 3 H
(H-10); 1.49 s, 3 H (H-10′); 1.46–1.58 m , 1 H (H-4); 2.35 d, 1 H, J(6,5) = 2.7 (H-6); 2.37 dd, 1 H,
J(2,2′) = 15.3, J(2,3) = 7.1 (H-2); 2.53 dd, 1 H, J(2,2′) = 15.3, J(2′,3) = 7.1 (H-2′); 3.49–3.65 m
br, 2 H (H-11); 3.71 s, 3 H (OCH3); 3.80–4.20 m br, 2 H (H-11′); 4.20–4.35 m , 2 H (H-5, H-3);
7.20–7.45 m br, 10 H (H-13, H-14, H-15). Note: H-4′ was n ot observed. 13C NMR: 19.12
(C-10), 29.65 (C-8), 30.08 (C-10′), 37.14 (C-7), 37.41 (C-4), 41.28 (C-2), 51.63 (OCH3),
56.00–58.00 (br C-11), 66.82 (C-6), 67.80 (C-3), 68.86 (C-5), 98.84 (C-9), 126.82 (C-14),
128.06 (C-13), 129.31 (br C-15), 140.00–141.00 (br C-12), 171.44 (C-1). MS (70 eV, m/z
(rel.%)): 453 (0.2) [M+], 438 (3) [M+ – CH3], 396 (39) [M+ – C(CH3)3], 378 (4) [396 – H2O],
364 (3) [396+ – CH3OH], 338 (14), 266 (40) [C19H24N+], 246 (5), 210 (19), 181 (7), 91 (100)
[C7H7+], 59 (5), 57 (4) [C4H9+], 43 (5), 41 (5). HRMS C24H30NO4 (M+ – C4H9) calculated:
396.2175; foun d: 396.2175.
Methyl (4S,6R)-(–)-6-[(1S)-(dibenzylamino)-2-phenylethyl]-2,2-dimethyl-1,3-dioxane-4-acetate
((S,S,R)-17c): 0.56 g (81%) yield from dih ydroxyester 11c after colum n ch rom atograph y (sil-
ica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF 0.38 (ligh t petro-
leum /dieth yl eth er, 4:1); [α ]2D0 –25.9 (c 0.7, CH2Cl2); de > 96%, determ in ed by NMR; ee >
96%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral
cosolven t (6 equiv.). IR (film ): 3085, 3062, 3026, 2993, 2949, 2801, 1949, 1872, 1808, 1740
(COOMe), 1603, 1495, 1454, 1438, 1381, 1315, 1260, 1201, 1168, 1120, 1076, 1029, 983,
946, 699. 1H NMR: 1.06 ddd, 1 H, J(4,4′) = 12.6, J(4,5) = 11.8, J(4,3) = 11.2 (H-4); 1.34 s, 3 H
(H-13); 1.50 s, 3 H (H-13′); 1.56 ddd, 1 H, J(4,4′) = 12.6, J(4′,5) = 2.5, J(4′,3) = 2.2 (H-4′); 2.33
dd, 1 H, J(2,2′) = 15.4, J(2,3) = 5.8 (H-2); 2.49 dd, 1 H, J(2,2′) = 15.4, J(2′,3) = 7.1 (H-2′); 2.82
ddd, 1 H, J(6,7) = 8.2, J(6,7′) = 4.9, J(6,5) = 4.1 (H-6); 2.92 dd, 1 H, J(7,7′) = 14.3, J(7′,6) = 4.9
(H-7′); 2.97 dd, 1 H, J(7,7′) = 14.3, J(7,6) = 8.2 (H-7); 3.63 d br, 2 H, J(14,14′) = 14.0 (H-14);
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

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Enders, Burkamp:
3.68 s, 3 H (OCH3); 3.70 d br, 2 H, J(14,14′) = 14.0 (H-14′); 4.21 ddd, 1 H, J(5,4) = 11.8,
J(5,6) = 4.1, J(5,4′) = 2.5 (H-5); 4.30 dddd, 1 H, J(3,4) = 11.2, J(3,2′) = 7.1, J(3,2) = 5.8, J(3,4′) =
2.2 (H-3); 7.10–7.28 m , 15 H (H-9, H-10, H-11, H-16, H-17, H-18). 13C NMR: 19.67 (C-13),
30.02 (C-13′), 32.09 (C-7), 34.84 (C-4), 41.35 (C-2), 51.64 (OCH3), 54.63 (C-14), 63.25 (C-6),
66.26 (C-3), 69.04 (C-5), 98.70 (C-12), 125.58 (C-10), 126.72 (C-17), 128.00 (C-9), 128.08
(C-16), 128.65 (C-11), 129.72 (C-18), 140.00 (C-8), 141.59 (C-15), 171.46 (C-1). MS (70 eV,
m/z (rel.%)): 453 (0.2) [M+], 438 (3) [M+ – CH3], 396 (39) [M+ – C(CH3)3], 378 (4) [396 –
H2O], 364 (3) [396+ – CH3OH], 338 (14), 266 (40) [C19H24N+], 246 (5), 210 (19), 181 (7), 91
(100) [C7H7+], 59 (5), 57 (4) [C4H9+], 43 (5), 41 (5). HRMS C24H30NO4 (M+ – C4H9) calcu-
lated: 396.2175; foun d: 396.2175.
Methyl (4S,6R)-(+)-6-[(1S)-(tert-butyldimethylsilyl)-2-phenylethyl]-2,2-dimethyl-1,3-dioxane-
4-acetate ((S,S,R)-17e): 0.61 g (90%) yield from dih ydroxyester 11e after colum n ch rom atog-
raph y (silica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF 0.48 (ligh t
petroleum /dieth yl eth er, 4:1); [α ]D20 +34.3 (c 0.8, CH2Cl2); de > 96%, determ in ed by NMR; ee
> 93%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol as ch iral
cosolven t (6 equiv.). IR (film ): 3084, 3062, 3025, 2992, 2954, 2930, 2882, 2856, 1945, 1875,
1743 (COOMe), 1602, 1464, 1455, 1438, 1380, 1362, 1326, 1325, 1258, 1200, 1167, 1120,
1102, 1050, 1032, 1002, 953, 873, 824, 809, 767, 699. 1H NMR: 0.04 s, 3 H (H-13); 0.08 s,
3 H (H-13′); 0.93 s, 9 H (H-16); 1.14–1.32 m , 2 H (H-4, H-4′); 1.35 s br, 6 H (H-13, H-13′);
1.46 ddd, 1 H, J(6,7) = 7.4, J(6,7′) = 5.8, J(6,5) = 3.0 (H-6); 2.23 dd, 1 H, J(2,2′) = 15.7, J(2,3) =
5.8 (H-2); 2.41 dd, 1 H, J(2,2′) = 15.7, J(2′,3) = 7.4 (H-2′); 2.80–2.82 m , 2 H (H-7, H-7′); 3.64
s, 3 H (OCH3); 4.05 m , 1 H (H-5); 4.14 m , 1 H (H-3); 7.10–7.30 m , 5 H (H-9, H-10, H-11).
13C NMR: –5.65 (C-14), –5.33 (C-14′), 17.66 (C-15), 19.68 (C-13), 27.38 (C-16), 29.74 (C-6),
29.99 (C-13′), 31.60 (C-7), 35.18 (C-4), 41.24 (C-2), 51.55 (OCH3), 66.21 (C-3), 69.85 (C-5),
98.60 (C-12), 125.52 (C-10), 128.24 (C-9), 128.37 (C-11), 143.76 (C-8), 171.52 (C-1). MS (70 eV,
m/z (rel.%)): 406 (0.2) [M+], 391 (1) [M+ – CH3], 349 (1) [M+ – C4H9], 291 (100) [349+
–
CH3COCH3], 259 (12) [291+ – CH3OH], 217 (2), 191 (8), 185 (8), 167 (9), 157 (6), 143 (36),
129 (8), 128 (6), 117 (6), 115 (9) [TBDMS+], 91 (28) [C7H7+], 89 (28), 75 (29) [C2H7OSi+], 73
(29) [TMS+], 59 (10), 57 (8) [C4H9+], 55 (7), 43 (7), 41 (9). HRMS C22H35O4Si (M+ – CH3) cal-
culated: 391.2305; foun d: 391.2307.
Methyl (4S,6R)-(+)-6-[(1S)-(tert-butyldimethylsilyl)-2-(2,4-dichlorophenyl)ethyl]-2,2-dimethyl-
1,3-dioxane-4-acetate ((S,S,R)-17f): 0.59 g (90%) yield from dih ydroxyester 11f after colum n
ch rom atograph y (silica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF
0.64 (ligh t petroleum /dieth yl eth er, 4:1); [α ]2D0 +36.5 (c 0.8, CH2Cl2); de = 95%, determ in ed
by NMR; ee = 95%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoroeth an -1-ol
as ch iral cosolven t (6 equiv.). IR (film ): 3095, 3060, 3020, 2954, 2929, 2883, 2857, 1900,
1729 (COOMe), 1586, 1559, 1472, 1439, 1387, 1363, 1338, 1310, 1255, 1201, 1169, 1137,
1101, 1050, 1008, 865, 825, 810, 715, 702, 689, 667. 1H NMR: 0.05 s, 3 H (H-15); 0.08 s, 3 H
(H-15′); 0.93 s, 9 H (H-18); 1.02 ddd, 1 H, J(4,4′) = 12.6, J(4,5) = 11.6, J(4,3) = 11.5 (H-4);
1.22 ddd, 1 H, J(4,4′) = 12.6, J(4′,3) = 2.7, J(4′,5) = 2.4 (H-4′); 1.34 s, 3 H (H-15); 1.36 s, 3 H
(H-15′); 1.52 ddd, 1 H, J(6,7) = 11.0, J(6,7′) = 3.1, J(6,5) = 2.7 (H-6); 2.20 dd, 1 H, J(2,2′) =
15.6, J(2,3) = 5.8 (H-2); 2.37 dd, 1 H, J(2,2′) = 15.6, J(2′,3) = 7.0 (H-2′); 2.77 dd, 1 H, J(7,7′) =
15.6, J(7′,6) = 3.1 (H-7′); 2.98 dd, 1 H, J(7,7′) = 15.6, J(7,6) = 11.0 (H-7); 3.64 s, 3 H (OCH3);
4.03 ddd, 1 H, J(5,4) = 11.6, J(5,6) = 2.7, J(5,4′) = 2.4 (H-5); 4.13 dddd, 1 H, J(3,4) = 11.5,
J(3,2′) = 7.0, J(3,2) = 5.8, J(3,4′) = 2.7 (H-3); 7.16 dd, 1 H, J(12,13) = 8.2, J(12,10) = 2.1
(H-12); 7.25 d, 1 H, J(13,12) = 8.2 (H-13); 7.33 d, 1 H, J(10,12) = 2.1 (H-10). 13C NMR: –5.65
(C-16), –5.49 (C-16′), 17.64 (C-17), 19.61 (C-15), 27.35 (C-18), 28.45 (C-6), 28.99 (C-7),
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New Analogues of Mevinic Acids
1003
29.99 (C-15′), 35.43 (C-4), 41.16 (C-2), 51.57 (OCH3), 66.17 (C-3), 69.48 (C-5), 98.70 (C-14),
126.69 (C-12), 129.19 (C-13), 131.61 (C-10), 131.83 (C-11), 134.58 (C-9), 139.72 (C-8),
171.44 (C-1). MS (70 eV, m/z (rel.%): 459 (0.8) [M+ – CH3], 401 (3) [M+ – C3H5O2], 359 (74)
[M+ – C4H9 – CH3COCH3], 327 (8) [359+ – CH3OH], 259 (5) [C11H13Cl2OSi+], 225 (4), 211
(14), 203 (8), 185 (8), 159 (34), 133 (7), 119 (45), 115 (13) [TBDMS+], 105 (6), 93 (17), 89
(100) [C4H7O2+], 75 (69) [C2H7OSi+], 73 (87) [TMS+], 69 (6), 57 (10) [C4H9+], 43 (22), 41
(15.5). For C23H36Cl2O4Si (475.5) calculated: 58.09% C, 7.63% H; foun d: 58.47% C, 7.71% H.
Methyl (4S,6R)-(+)-6-[(1S)-(tert-butylsulfanyl)-2-phenylethyl]-2,2-dimethyl-1,3-dioxane-4-acetate
((S,S,R)-17i): 0.52 g (83%) yield from dih ydroxyester 11i after colum n ch rom atograph y (sil-
ica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF 0.50 (ligh t petroleum /
dieth yl eth er, 4:1); m .p.: 110 °C (pen tan e); [α ]2D0 +15.5 (c 0.52, CH2Cl2). de > 96%, deter-
m in ed by NMR; ee = 93%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-2,2,2-trifluoro-
eth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3084, 3066, 3027, 2980, 2962, 2932,
2874, 1937, 1861, 1736 (COOMe), 1605, 1495, 1473, 1460, 1445, 1409, 1391, 1380, 1364,
1322, 1252, 1230, 1198, 1166, 1148, 1126, 1065, 1039, 1030, 993, 978, 945, 925, 841, 810,
786, 750, 695. 1H NMR: 1.15 s, 9 H (H-15); 1.29 ddd, 1 H, J(4,4′) = 12.6, J(4,3) = 12.1,
J(4,5) = 11.3 (H-4); 1.38 s, 3 H (H-13); 1.41 s, 3 H (H-13′); 1.99 ddd, 1 H, J(4,4′) = 12.6, J(4′,5)
= 2.5, J(4′,3) = 2.2 (H-4′); 2.40 dd, 1 H, J(2,2′) = 15.4, J(2,3) = 5.5 (H-2); 2.56 dd, 1 H, J(2,2′) =
15.4, J(2′,3) = 7.1 (H-2′); 2.74 dt, 1 H, J(6,7) = 7.4, J(6,7′) = J(6,5) = 4.7 (H-6); 2.85 dd, 1 H,
J(7,7′) = 13.5, J(7,6) = 7.4 (H-7); 3.05 dd, 1 H, J(7,7′) = 13.5, J(7′,6) = 4.7 (H-7′); 3.68 s, 3 H
(OCH3); 3.69 ddd, 1 H, J(5,4) = 11.3, J(5,6) = 4.7, J(5,4′) = 2.5 (H-5); 4.22 dddd, 1 H, J(3,4) =
12.1, J(3,2′) = 7.1, J(3,2) = 5.5, J(3,4′) = 2.2 (H-3); 7.19–7.32 m , 5 H (H-9, H-10, H-11).
13C NMR: 19.73 (C-13), 29.96 (C-13′), 31.49 (C-15), 34.08 (C-4), 39.07 (C-7), 41.31 (C-2),
43.42 (C-14), 49.27 (C-6), 51.61 (OCH3), 66.24 (C-3), 70.89 (C-5), 99.09 (C-12), 126.11
(C-10), 127.75 (C-9), 130.42 (C-11), 139.21 (C-8), 171.36 (COOMe). MS (70 eV, m/z (rel.%)):
380 (9) [M+], 365 (2) [M+ – CH3], 309 (4) [365+ – C4H8], 187 (57) [C9H15O3+], 175 (10), 169
(15), 155 (4), 137 (6), 129 (100) [187+ – CH3COCH3], 101 (16), 97 (24), 91 (22) [C7H7+], 59
(31), 57 (30) [C4H9+], 43 (14), 41 (13). HRMS C21H32O4S (M+) calculated: 380.2021; foun d:
380.2023.
Methyl (4S,6R)-(+)-6-[(1S)-(tert-butylsulfanyl)-2-(2,4-dichlorophenyl)ethyl]-2,2-dimethyl-1,3-dioxane-
4-acetate ((S,S,R)-17j): 0.48 g (67%) yield from dih ydroxyester 11j after colum n ch rom atogra-
ph y (silica gel, ligh t petroleum /dieth yl eth er, 4:1) followin g procedure IX; RF 0.85 (ligh t pe-
troleum /dieth yl eth er, 2:1); m .p. 90 °C (pen tan e); [α ]2D0 +8.8 (c 0.74, CH2Cl2); de > 96%,
determ in ed by NMR; ee
=
94%, determ in ed by 1H NMR with (–)-(R)-1-(9-an th ryl)-
2,2,2-trifluoroeth an -1-ol as ch iral cosolven t (6 equiv.). IR (film ): 3069, 3039, 2993, 2981,
2969, 2949, 2935, 2866, 1742 (COOMe), 1655, 1637, 1587, 1559, 1474, 1439, 1381, 1365,
1320, 1263, 1251, 1232, 1198, 1168, 1148, 1126, 1095, 1070, 1051, 1039, 999, 975, 941,
887, 875, 845, 743 (m ). 1H NMR: 1.01 s, 9 H (H-17); 1.37 s, 3 H (H-15); 1.44 s, 3 H (H-15′);
1.44 ddd, 1 H, J(4,4′) = 12.5, J(4,5) = 11.6, J(4,3) = 11.5 (H-4); 1.88 ddd, 1 H, J(4,4′) = 12.5,
J(4′,5) = 2.4, J(4′,3) = 2.1 (H-4′); 2.43 dd, 1 H, J(2,2′) = 15.6, J(2,3) = 5.8 (H-2); 2.53 dd, 1 H,
J(7,7′) = 13.7, J(7,6) = 10.4 (H-7); 2.58 dd, 1 H, J(2,2′) = 15.6, J(2′,3) = 7.0 (H-2′); 2.80 ddd, 1 H,
J(6,7) = 10.4, J(6,5) = 5.5, J(6,7′) = 4.0 (H-6); 3.34 dd, 1 H, J(7,7′) = 13.7, J(7′,6) = 4.0 (H-7′);
3.70 s, 3 H (OCH3); 3.93 ddd, 1 H, J(5,4) = 11.6, J(5,6) = 5.5, J(5,4′) = 2.4 (H-5); 4.31 dddd, 1 H,
J(3,4) = 11.5, J(3,2′) = 7.0, J(3,2) = 5.8, J(3,4′) = 2.1 (H-3); 7.16 dd, 1 H, J(12,13) = 8.2,
J(12,10) = 2.2 (H-12); 7.27 d, 1 H, J(13,12) = 8.2 (H-13); 7.33 d, 1 H, J(12,10) = 2.2 (H-10).
13C NMR: 19.66 (C-15), 29.81 (C-15′), 31.24 (C-16), 33.80 (C-4), 36.04 (C-7), 41.27 (C-2),
43.25 (C-16), 46.92 (C-6), 51.67 (OCH3), 66.17 (C-3), 73.16 (C-5), 99.14 (C-14), 126.35
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

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Enders, Burkamp:
(C-12), 128.84 (C-13), 132.65 (C-11), 134.30 (C-10), 135.04 (C-9), 136.23 (C-8), 171.47 (C-1).
MS (70 eV, m/z (rel.%): 448 (0.4) [M+], 413 (12) [M+ – Cl], 359 (1) [M+ – SC(CH3)3], 317 (2)
[359+ – H2C=C=O], 281 (12), 187 (26) [C9H15O4+], 169 (11) [187+ – H2O], 159 (8) [C7H5Cl2+],
129 (100) [187+ – CH3COCH3], 101 (17), 97 (24), 59 (36), 57 (42) [C4H9+], 43 (16), 41 (17).
For C21H30Cl2O4S (449.4) calculated: 56.12% C, 6.73% H; foun d: 56.46% C, 6.88% H.
This work was supported by the Fonds der Chemischen Industrie and by the Deutsche
Forschungsgemeinschaft (Sonderforschungsbereich 380 and Leibniz award). We thank the companies
BASF AG, Bayer AG, Degussa AG, Hoechst AG and W acker AG for their donation of chemicals.
F. Burkamp thanks the Fonds der Chemischen Industrie for a fellowship.
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