Chemoenzymatic Syntheses of Some Analogues of the Tricarbocyclic Core of the Anti-Bacterial Agent Platencin and the Biological Evaluation of Certain of their N-Arylpropionamide Derivatives

Article abstract of DOI:10.1071/CH18145

A range of structural variations on the tricarbocyclic core 2 of the anti-bacterial agent platencin 1, including those represented by compounds 14, 15, and 27, have been prepared and certain of these elaborated, through substrate-controlled enolate alkylation reactions, to analogues of the natural product. Preliminary biological evaluation of these analogues revealed that they are only weakly active anti-infective agents.

Full text of DOI:10.1071/CH18145

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
https://doi.org/10.1071/CH18145
Chemoenzymatic Syntheses of Some Analogues of the
Tricarbocyclic Core of the Anti-Bacterial Agent Platencin
and the Biological Evaluation of Certain of their
N-Arylpropionamide Derivatives*
A
A
B
Rehmani N. Muhammad, Ee Ling Chang, Alistair G. Draffan,
A
A
A C
,
Anthony C. Willis, Paul D. Carr, and Martin G. Banwell
A
Research School of Chemistry, Institute of Advanced Studies, The Australian National
University, Canberra, ACT 2601, Australia.
B
Biota Scientific Management Pty Ltd, Melbourne, Vic. 3168, Australia.
C
Corresponding author. Email: Martin.Banwell@anu.edu.au
A range of structural variations on the tricarbocyclic core 2 of the anti-bacterial agent platencin 1, including those
represented by compounds 14, 15, and 27, have been prepared and certain of these elaborated, through substrate-controlled
enolate alkylation reactions, to analogues of the natural product. Preliminary biological evaluation of these analogues
revealed that they are only weakly active anti-infective agents.
Manuscript received: 6 April 2018.
Manuscript accepted: 18 May 2018.
Published online:
6 July 2018.
Introduction
OH
O
HO2C
The emergence of drug-resistant bacteria has been described as
one of the most significant threats facing humankind at the
present time.[1] In seeking to address this profound challenge
through the identification of new anti-bacterial agents posses-
sing novel modes of action, scientists at Merck & Co. isolated
platencin 1 from a strain of the soil bacterium Streptomyces
platensis.[2] It was established that this natural product inhibited
certain enzymes associated with bacterial fatty acid biosyn-
thesis and thus interfered with the assembly of their cell
walls.[2] As a result, compound 1 acts against a wide range of
bacteria including methicillin-resistant Staphylococcus aureus
(MRSA), vancomycin-resistant enterococci (VRE), and
Mycobacterium tuberculosis. Such features, together with its
lack of toxicity to mammalian systems, have created significant
interest in platencin as a lead for the development of new
generation anti-bacterial agents.[2,3] Accordingly, extensive
efforts have been directed towards its synthesis and a range of
approaches has been reported and reviewed.[1,4]
HO
N
O
H
OH
OH
O
H
H
I
1
2
3
Chart 1.
derivative 4 of diol 3, was subjected to a Negishi-type cross-
coupling with the racemic organozinc species 5 and so formed
the triene 6 as a ,1 : 1 mixture of diastereoisomers in 85 %
combined yield. Despite the absence of an activating group, the
side-chain double bond within compound 6 engaged in a
remarkably facile, thermally induced, and diastereoselective
Type 1 intramolecular Diels–Alder (IMDA) cycloaddition reac-
tion with the diene moiety embedded in the cis-1,2-dihydroca-
techol residue and thus affording adduct 7 in 89 % yield. A series
of twelve relatively conventional functional group interconver-
sions then allowed for the completion of the synthesis of
compound 2.
In an effort to establish a shorter route to platencin, the
pathway shown in Scheme 2 was developed.[8] Thus, acetonide
4 was engaged in a Stille cross-coupling reaction with a more
elaborate side-chain, namely the Z-configured alkenylstannane
8 wherein the associated stereogenic centre was constructed
using a chiral auxiliary-based approach. While the so-formed
In 2008 we detailed[5] an enantioselective synthesis of
compound 2 that embodies the tricarbocyclic core of platencin
and that has been elaborated, by Nicolaou and-co-workers,[6] to
platencin itself. The starting material used in our work was the
cis-1,2-dihydrocatechol 3. This is obtained in homochiral form
through the whole-cell biotransformation of iodobenzene using
the genetically engineered microorganism E. coli JM109
(pDTG601) that overexpresses the responsible enzyme, namely
toluene dioxygenase (Chart 1).[7]
The key features of our reaction sequence[5] leading to enone
2 are shown in Scheme 1. Thus, the readily obtained acetonide
*Dedicated to the memory of Professor Sir Derek Barton and in recognition of his seminal contributions to so many aspects of organic chemistry.
Journal compilation ꢀ CSIRO 2018
www.publish.csiro.au/journals/ajc

B
R. N. Muhammad et al.
tetra-ene 9 (80 %) failed to engage in the hoped-for IMDA
cycloaddition reaction, the readily derived ketone 10 (53 %) did
so and thus produced adduct 11 in 79 % yield. The differing
behaviours of compounds 9 and 10 towards this critical cyclo-
addition process may reflect the conformational preferences
within the latter substrate that predispose it, through pre-orga-
nisational effects, towards reaction. Adduct 11 could be elabo-
rated to platencin over 13-steps, although on exposing this
compound to hydrogen in the presence of Pd on C not only
did cleavage of the benzyl ether and hydrogenation of the
isolated C=C double bond take place (both desired processes)
but the double bond of the enone moiety was also reduced (an
undesired process). As a result, two additional steps were
required to reinstate the latter bond.
In another study, the outcomes of which we reported
recently,[9] compound 2 was elaborated, including via sub-
strate-controlled enolate alkylation reactions, into platencin
and by a slightly shorter route than that involving the manipula-
tion of the IMDA adduct 11.
In an effort to improve the pharmacokinetic properties of
platencin, considerable effort has been directed towards the
synthesis of analogues.[2b] Structure–activity relationship stud-
ies in this domain have revealed that modest variations in the
tricarbocyclic core 2 of platencin can be tolerated but that even
minor modifications to the 3-amino-2,4-dihydroxybenzoic acid
residue are deleterious. The impact of varying the nature of the
propionamide linker between these two motifs remains to be
established.
O
O
I
4
O
TBDMSO
H
ꢀ
Pd0
toluene
O
85 %
O
112°C
89 %
ZnI
O
7
OTBDMS
OTBDMS
6
12 steps
5
O
H
2
Scheme 1.
O
O
I
4
O
O
O
O
Pd0
DMP
53 %
OH
O
ꢀ
80 %
OH SnBu3
9
10
BnO
BnO
BnO
8
OBn
toluene
112ꢁC
O
H
79 %
O
O
11
Scheme 2.

Chemoenzymatic Syntheses of Some Analogues of Platencin
C
In this report we now detail efforts to apply the ‘intelligence’
gathered during the above-mentioned total synthesis studies on
compound 1 to the production of various analogues of the
tricarbocyclic core of the natural product as well as the elabora-
tion of certain of these to ‘fully fledged’ variants of platencin for
the purposes of subjecting them to biological evaluation. Among
the various analogues of enone 2 targeted in preliminary
synthetic studies were compounds 12–15 (Chart 2). These were
sought because of their anticipated ease of access using our
established chemical protocols and the lack of any prior studies
on most of them. The approaches to these compounds are
detailed in the following section, as are the outcomes of studies
on the conversion of certain of these into N-arylpropionamide
derivatives for the purposes of assessing their anti-bacterial
effects.
Results and Discussion
Synthetic Studies
The approach taken in efforts to prepare our initial target
compound 12 is shown in Scheme 3 and involved attempting to
implement an IMDA reaction analogous to that employed in
obtaining compound 2 (Scheme 1). Thus, the previously repor-
ted[5] diene 16 was subjected to mono-hydroboration using
9-borabicyclo[3.3.1]nonane (9-BBN) and the ensuing organo-
borane oxidised in situ to give, in racemic form, the 18 alcohol
17[10] in 75% yield. The reaction of compound 17 with triphe-
nylphosphine in the presence of molecular iodine gave the
anticipated Appel-type product 18 (79 %) and the organozinc
species derived from this was cross-coupled with the iododiene
4 to give the triene 19 (65 %) as a ,1 : 1 mixture of diasteroi-
somers. Treatment of this last compound with tetra-n-buty-
lammonium fluoride (TBAF) then afforded the corresponding
alcohol 20. Disappointingly, and despite examining a range of
conditions, neither ether 19 nor the corresponding alcohol 20
participated in IMDA cycloaddition reactions to give the hoped-
for adducts 21 and 22, respectively. Such outcomes are attributed
to adverse entropic effects arising from the longer linker (relative
to congeners 6 and 10) joining the diene and dienophilic residues
in compounds 19 and 20. Accordingly, alternate routes to such
seven-membered ring-containing compounds were pursued.
Our failure to establish a direct route to seven-membered ring
homologues of compound 2 prompted exploration of an
approach wherein cyclopropanated derivatives of the parent
framework would be assembled with the intention of subjecting
these to ring-expansion processes. In a first attempt to imple-
ment such ideas, the previously reported[9] cyclohexenone 23
(Scheme 4), and a readily obtained derivative of compound 7,
was subjected to reaction with the Corey–Chaykovsky ylide[11]
in the hope of effecting a nucleophilic cyclopropanation
O
O
H
H
H
O
O
H
O
O
12
13
O
H
H
O
O
O
O
O
14
15
Chart 2.
I
OH
(i) 9-BBN, THF
I2
22ꢁC, 1 h
Ph3P
OTBDMS
OTBDMS
C6H6/Et2O
0 to 22ꢁC
2.5 h, 79 %
OTBDMS
•
(ii) NaBO3 4H2O
22ꢁC, 1 h
75 %
18
16
17
O
t-BuLi, Znl2
(Ph3P)4Pd
THF, 22ꢁC, 3 h
O
65 %
I
4
O
RO
H
O
see text
X
O
OR
O
TBAF, THF
0 to 22ꢁC
8.5 h, 51 %
21 (R ꢂ TBDMS)
22 (R ꢂ H)
19 (R ꢂ TBDMS)
20 (R ꢂ H)
Scheme 3.

D
R. N. Muhammad et al.
O
H
H
Various efforts, involving the use of both Brønsted–Lowry
and Lewis acids, were made to effect the ring-expansion of
compounds 26, 27, and 28 but these either returned the starting
materials or produced complex mixtures of products. As such,
attempts to convert these cyclopropannulated cyclohexanes into
seven-membered ring-containing systems such as 22 were
abandoned.
O
trimethylsulfox-
onium iodide
O
O
NaH, DMSO
22 to 50ꢁC, 3 h
see text
O
O
24
23
NaBH4
In seeking to obtain the rearranged enone 14, another of our
original targets, the nucleophilic epoxidation of enone 23
(Scheme 5) was explored. This proceeded effectively on expo-
sure of the substrate to alkaline hydrogen peroxide and thus
afforded compound 29 in 79 % yield. While the configuration of
this epoxide proved to be of little consequence in terms of the
outcomes of the subsequent Wharton rearrangement,[15] it is
presumed to possesses the illustrated stereochemistry as a result
of preferential b-face addition of the hydroperoxy anion to the
•
CeCl3 7H2O
MeOH, 22ꢁC
2.5 h, 87 %
HO
H
HO
H
H
CH2l2, Znl2
O
O
O
CH2Cl2
0 to 22ꢁC
1.5 h, 77 %
H
enone moiety of the substrate. That said, inspection of the 13
C
O
NMR spectrum of this product suggested that small amounts
(,10 %) of the other diastereoisomer were also likely to have
been formed in the reaction. On treating this epoxy-ketone with
hydrazine in the presence of acetic acid the anticipated reaction
took place and so afforded the allylic alcohol 30 in 71 % yield.
DMP-mediated oxidation of this last compound then gave the
rearranged enone 14 (97 %), the spectroscopic features of which
were similar but not identical with those of precursor 23.
Perhaps the most notable difference was evident in the 1H
NMR spectra. In the spectrum of compound 14 the resonance
due to the b-proton of the enone moiety appeared at d 6.83 as a
doublet of doublet of doublets (J 10.2, 5.8, and 2.2) while for
precursor 23 this resonated at d 6.89 as a doublet (J 10.1).[9]
In another conjugate addition process (Scheme 6), compound
23 was treated with the Gilman reagent and thus afforded the
b-methylated cyclohexanone 31 in 71 % yield. On exposing this
compound to a mixture of 2-iodoxybenzoic acid (IBX) and
4-methoxypyridine N-oxide (MPO), under conditions defined
26
25
DMP
CH2Cl2
22ꢁC, 2.5 h
95 %
O
O
H
H
H
Mel
KHMDS
H
O
O
O
HMPA
ꢃ78 to 0ꢁC
2.5 h, 75 %
H
H
O
28
27
Scheme 4.
reaction. However, this did not occur. Rather, a complex
reaction mixture was obtained and spectroscopic analysis of
this indicated the presence of olefinic protons and the absence of
a carbonyl group suggesting the spirocyclic epoxide 24 may
have been formed (the illustrated configuration at the spirocyc-
lic centre is suggested on the basis that nucleophilic additions to
substrates such as 23 take place preferentially from the sterically
more accessible b-face). However, pure samples of compound
24 could not be obtained and so exhaustive characterisation of
this product was not possible.
by Nicolaou and co-workers,[16]
a chromatographically
inseparable 2 : 3 mixture of the methylated and regioisomeric
cyclohexenones 15 and 32 was obtained in 79 % yield. Interest-
ingly, this mixture of compounds proved to be crystalline and an
X-ray analysis revealed the presence of one molecule of each of
compounds 15 and 32 in the unit cell. Once again, details of this
O
O
H
H
H2O2, NaOH
MeOH
A
directed electrophilic cyclopropanation pathway
H
O
O
(Scheme 4) was also pursued in efforts to obtain the target ring
system. Thus, Luche reduction[12] of enone 23 afforded the a-
configured allylic alcohol 25 (87 %) stereoselectively and on
subjecting this to a Furukawa-modified Simmons–Smith cyclo-
propanation reaction[13] compound 26 was obtained as a single
diastereoisomer in 77 % yield. Oxidation of alcohol 26 with the
Dess–Martin periodinane (DMP)[14] then gave the correspond-
ing cyclopropyl ketone 27 (95 %) and on treatment of the
derived enolate with methyl iodide the mono-methylated ketone
28 (75 %) was obtained as a crystalline solid. A single-crystal X-
ray analysis of this material served to confirm the illustrated
structure. Details of this analysis, including the derived ORTEP
diagram, are provided in the Supplementary Material.
O
0 to 22ꢁC
2 h, 79 %
H
O
O
23
29
•
H2NNH2 H2O
AcOH
0 to 22ꢁC 2 h, 71 %
DMP
CH2Cl2
H
H
O
O
The outcomes of the conversions 23 - 25 and 27 - 28
shown in Scheme 4 serve to emphasise that while b-face attack on
such substrates tends to be favoured, a-face addition processes
(such as 25 - 26) can still be effected through reagent complex-
ation by appropriately (a) configured directing groups.
22ꢁC, 2.5 h
97 %
O
O
HO
O
14
30
Scheme 5.

Chemoenzymatic Syntheses of Some Analogues of Platencin
E
O
O
MeLi
Cul
H
O
H
O
the total synthesis of platencin and a representative set of
outcomes is shown in Scheme 8.
Et2O
ꢃ78ꢁC
1.5 h, 71 %
Thus, the enolate obtained on treating enone 36 with potassium
hexamethyldisilazide (KHMDS) at ꢀ788C was treated with
methyl iodide and the ensuing mixture allowed to warm to 08C
over 2.5 h. After work-up and chromatography three products,
namelythe mono-methylated compounds 37 (23 %) and 38 (51 %)
together with the gem-dimethylated congener 39 (7 %), were
obtained and the structure of the first of these was confirmed by
single-crystal X-ray analysis. On treating the mono-methylated
system 38 with t-butyl acrylate in the presence of potassium t-
butoxide, the anticipated Michael addition reaction took place and
so produced propionate ester 40 (57 %) as the major reaction
product. NMR analysis of the crude reaction product also sug-
gested the presence of traces of epimer 41 but this could not be
isolated in pure form in sufficient quantities to allow for its
independent spectroscopic characterisation. The illustrated
O
O
23
31
IBX
MPO
DMSO
22ꢁC, 16 h
79 %
O
O
H
ꢀ
O
O
O
O
15
32
O
Scheme 6.
O
O
analysis are provided in the Experimental section and the
Supplementary Material.
36
In an effort to establish the effect that other, adjacent function-
alities might have on the regioselectivities of these types of
dehydrogenation reactions, the unsaturated cyclohexanone 33
(Scheme 7), which is readily prepared from IMDA adduct 7 (see
Experimental for details), was also subjected to reaction with IBX
and MPO. Under such conditions essentially the same outcome
was observed, namely a 1 : 3 mixture of the regioisomeric die-
nones 34 and35 wasformed in 86 % combined yield. Gratifyingly,
these could be separated chromatographically and each was
subjected to single-crystal X-ray analysis, details of which are
provided in the Supplementary Material.
HMPA
MeI
ꢃ78 to 0ꢁC
KHMDS
2.5 h
O
O
ꢀ
R1
R2
O
O
O
O
Having established various protocols for manipulating the
cyclohexenone-containing core of platencin, our attention
turned to the application of enolate alkylation protocols so
as to determine how readily the a-methyl and propionic acid
‘side-chain’ groups seen in platencin could be installed in a
stereoselective manner. The protocols developed for this
purpose were, of course, informed by our earlier study[9] on
37 (R1 ꢂ Me, R2 ꢂ H) (23 %)
38 (R1 ꢂ H, R2 ꢂ Me) (51 %)
39
(7 %)
compound 38
t-butyl acrylate
t-BuOH
Et2O, 0ꢁC
0.7 h
t-BuOK
O
H
O
O
O
O
33
O
t-BuO
O
40
(57 %)
DMSO
IBX
MPO
22ꢁC, 16 h
ꢀ
O
O
O
H
O
O
ꢀ
O
O
t-BuO
O
O
O
41
(trace)
34
(21 %)
35
(65 %)
Scheme 8.
Scheme 7.

F
R. N. Muhammad et al.
configurations of the newly established quaternary carbons in
these esters are assigned on the basis that the major product of
reaction should be that in which the acrylate reacts preferentially at
the b-face of the enolate.
yl)oxidanyl (TEMPO). By such means the acyloin 44 was
obtained in 85 % yield and with noevidence for the co-production
of its regio-isomer. Acetylation of compound 44 was achieved
under conventional conditions and the resulting ester 45 (75 %)
was subjected to reductive deoxygenation using Torii’s low-
valent vanadium reagent[18] to afford the ketone 46 in 85% yield.
Chen and co-workers have reported[19] the elaboration of com-
pound 46, over three steps, into amide 47, the C-4 epimer of
platencin and a compound that displays somewhat weaker anti-
bacterial activity than the natural product.
Another aspect of our intelligence gathering activities in the
area was an investigation of the capacity to effect selective
manipulations of the acetonide moiety in systems incorporating
cyclohexenone and propionate residues using the repertoire of
transformations that we had employed earlier.[8,9] The substrate
we chose for such purposes was compound 42 (Scheme 9) that
had been obtained previously as a minor product from succes-
sive methylation and propionylation reactions of enone 23 using
the same conditions as described immediately above. Thus,
treating acetonide 42 with acidified DOWEX-50 resin in meth-
anol/THF/water at 658C for 36 h afforded diol 43 in 61 % yield
(at 79 % conversion). Gratifyingly, there was little evidence for
the competing cleavage of the t-butyl ester moiety under these
conditions. The selective oxidation of the hydroxy group remote
from the fully substituted bridgehead carbon of the bicyclo[2.2.2]
octane framework within compound 43 could be achieved using
Bobbitt’s reagent,[17] namely the sterically demanding oxammo-
nium salt derived from the p-toluenesulfonic acid-promoted
disproportionation of 4-NHAc-(2,2,6,6-tetramethylpiperidin-1-
In a series of related transformations, as shown in Scheme 10,
the enolate anion obtained by deprotonation of the previously
O
MeO
O
H
O
O
49
(72 %)
O
methyl acrylate
H
O
t-BuOK
ꢀ
Et2O, t-BuOK
ꢃ10ꢁC, 0.5 h
O
O
O
t-BuO
O
t-BuO
48
MeO
O
DOWEX-50
O
(Hꢀ form)
H
O
H
H
O
MeOH/water/THF
O
65ꢁC, 36 h
61 %
OH
OH
O
O
(@ 79 % conversion)
43
42
50
(14 %)
CH2Cl2
0 to 22ꢁC
2.5 h, 85 %
4-NHAc-TEMPO
compound 49
DOWEX-50
(Hꢀ form)
MeOH/water
65ꢁC, 56 h, 78 %
(@ 85 % conversion)
•
p-TsOH H2O
O
O
t-BuO
O
t-BuO
O
MeO
Ac2O
DMAP
MeO
4-NHAc-TEMPO
•
p-TsOH H2O
O
O
H
H
pyridine
22ꢁC, 3.5 h
75 %
O
O
H
H
O
O
CH2Cl2
0 to 22ꢁC
2.5 h, 93 %
O
OH
OH
OAc
OH
OH
44
45
51
52
BzCl
sonication
toluene
1 h, 83 %
•
VCl3 (THF)3
Zn
Et3N, DMAP
0 to 22ꢁC
16.5 h, 89 %
OH
O
HO2C
HO
O
O
O
t-BuO
N
MeO
MeO
O
H
literature
3 steps
Ph3P=CH2
O
H
O
O
H
H
H
O
O
THF, toluene
0 to 22 to ꢃ78ꢁC,
2 h, 71 %
OBz
OBz
46
47
54
53
Scheme 9.
Scheme 10.

Chemoenzymatic Syntheses of Some Analogues of Platencin
G
reported[9] mono-methylated enone 48 was reacted with methyl
acrylate and thus afforded a 5 : 1 mixture of the epimeric
propionic acid methyl esters 49 (72 %) and 50 (14 %). The
acetonide residue associated with the major product, which is
assumed to possess the illustrated b-configuration of the pro-
pionoate side-chain at C-4, could be cleaved under standard
conditions and the resulting diol 51 (78 % at 85 % conversion)
selectively oxidised using Bobbitt’s reagent[17] and thus
afforded acyloin 52 (93 %) that was itself esterified using
benzoyl chloride in the presence of 4-(N,N-dimethylamino)
pyridine (DMAP) and triethyamine to yield compound 53
(89 %). Selective Wittig methylenation of the non-conjugated
ketone residue within this last compound could be accomplished
under relatively conventional conditions and gave the allylic
ester 54 in 71 % yield.
The final focus of the present study was the conversion of
certain propionic acid ester derivatives of the tricarbocyclic core
framework, namely those incorporating an acetonide protecting
group, into the corresponding N-aryl amides for the purposes of
evaluating these as anti-infective agents. To such ends the
reaction sequence shown in Scheme 11 was pursued wherein
ester 49 was saponified using lithium hydroxide in aqueous THF
and the free-acid 55 (97 %) obtained on work-up coupled, under
conditions defined by Chen,[19] with the protected aminoben-
zoic acid derivative 56[19] in the presence of 1-[bis(dimethyla-
mino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid
hexafluorophos-phate (HATU)[20] to form the amide 57
(32 %). Finally, treatment of this TMSE-ester-containing com-
pound with tris(dimethylamino)sulfonium difluorotrimethylsi-
licate (TASF)[21] resulted in the formation of target 58, although
repeated chromatographic purification was required to obtain
material of appropriate quality and as a consequence this
compound was only obtained in 21 % yield.
free-acid 59 (95 %) obtained after acidic work-up was coupled
with the unprotected aminobenzoic acid 60 using 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDC) to provide the target
N-aryl amide 61 (27 %). The lack of a clean reaction associated
with this coupling reaction led us to conclude that despite the
need to employ an extra step (viz. a deprotection reaction) in the
reaction sequence, couplings involving the protected aminoben-
zoic acid 56 (rather than congener 60) lead to superior outcomes.
There are some modest differences in the spectroscopic data
sets derived from the epimeric platencin analogues 58 and 61,
perhaps the most conspicuous being in the high-field regions of
the 13C NMR spectra with the signals due to certain of the sp3-
hybridised carbons in the latter compound being more shielded
by the ‘overhanging’ N-aryl amide residue.
The final, acetonide-containing platencin analogue to be
prepared was the saturated equivalent of compound 58. This
was obtained by the simple route shown in Scheme 13. Specifi-
cally, the previously reported[8] acid 62 was coupled with
aniline 56 to afford amide 63 (14 %) that was deprotected with
TASF and delivered the third target analogue, namely com-
pound 64, in 15 % yield. Once again, the low yields observed in
this sequence derived from the need to subject each product to
extensive flash column chromatography so as to secure material
of adequate purity.
Biological Studies
The acetonide-containing platencin analogues 58, 61, and 64
were evaluated against a panel of Gram-positive bacteria
including Streptococcus pynogens ATCC 51339, Staphylococ-
cus aureus ATCC 19636, Enterococcus faecium ATCC 19434,
and Haemophilus influenzae ATCC 49247. Commercially
available platencin 1 and chloramphenicol were used as positive
controls. Such evaluations established that these analogues
displayed the same activity against S. pynogens and E. faecium
The C-4 epimer of compound 58 was prepared in a slightly
more direct manner as shown in Scheme 12. Thus, ester 50 was
saponified in the same way as congener 49 and the resulting
O
O
HO
O
MeO
O
O
O
LiOH
then H Oꢀ
HO
O
MeO
O
3
LiOH
H
O
H
then H3Oꢀ
THF, 50ꢁC
5 h, 95 %
H
O
H
O
THF, 50ꢁC
5 h, 97 %
O
O
O
O
O
50
59
49
55
HO2C
HO
OH
NH2
EDC, DMAP
DMF, 22ꢁC
36 h, 27 %
HATU
Et3N, DMF
22ꢁC, 16 h
32 %
TMSEO2C
OH
NH2
HO
60
56
OH
O
HO2C
HO2C
OH
O
TMSEO2C
HO
OH
O
HO
N
H
HO
N
N
H
TASF
H
O
DMF, 40ꢁC
1 h, 21 %
O
O
H
H
H
O
O
O
O
O
O
58
57
61
Scheme 11.
Scheme 12.

H
R. N. Muhammad et al.
O
Experimental
HO
O
General Experimental Procedures
Unless otherwise specified, 1H and 13C NMR spectra were
recorded at 188C in base-filtered CDCl3 on a Varian spec-
trometer operating at 400 MHz for proton and 100 MHz for
carbon nuclei. 1H NMR data are recorded as follows: chemical
shift (d) (multiplicity, coupling constant(s) J (Hz), relative
integral) where multiplicity is defined as: s ¼ singlet, d ¼
doublet, t ¼ triplet, q ¼ quartet, and m ¼ multiplet or combina-
tions of the above. The signal due to residual CHCl3 appearing at
dH 7.26 and the central resonance of the CDCl3 ‘triplet’
H
O
OH
TMSEO2C
HATU
ꢀ
O
NH2
HO
62
56
Et3N, DMF
22ꢁC, 16 h
14 %
appearing at dC 77.0 were used to reference H and 13C NMR
1
spectra, respectively. Infrared spectra (nmax) were recorded on a
Perkin–Elmer 1800 Series FTIR Spectrometer. Samples were
analysed as thin films on KBr plates. Low-resolution electro-
spray ionisation (ESI) mass spectra were recorded on a Micro-
mass LC-ZMD single quadrupole liquid chromatography–mass
spectrometer while high-resolution measurements were con-
ducted on an LCT Premier time-of-flight instrument. Low- and
high-resolution electron impact (EI) mass spectra were recorded
on an Autospec Premier Micromass magnetic-sector machine.
Optical rotations were recorded in CHCl3 at 208C on a Perkin
Elmer Model 343 Polarimeter. Melting points were measured on
an Optimelt automated melting point system and are uncor-
rected. Analytical thin layer chromatography (TLC) was per-
formed on aluminium-backed 0.2 mm thick silica gel 60 F254
plates as supplied by Merck. Eluted plates were visualised using
a 254 nm UV lamp and/or by treatment with a suitable dip fol-
lowed by heating. These dips included phosphomolybdic acid/
ceric sulfate/sulfuric acid (conc.)/water (37.5 g/7.5 g/37.5 g/
720 mL) or potassium permanganate/potassium carbonate/5 %
sodium hydroxide aqueous solution/water (3 g/20 g/5 mL/
300 mL). Flash chromatographic separations were carried out
following protocols defined by Still et al.[22] with silica gel 60
(40–63 mm) (silica) as the stationary phase and using the AR- or
HPLC-grade solvents indicated. Starting materials and reagents
were generally available from the Sigma–Aldrich, Merck, TCI,
Strem or Lancaster Chemical Companies and were used as
supplied. Drying agents and other inorganic salts were pur-
chased from the AJAX, BDH or Unilab Chemical Companies.
Tetrahydrofuran (THF), methanol, and dichloromethane
(DCM) were dried using a Glass Contour solvent purification
system that is based upon a technology originally described by
Grubbs et al.[23] Where necessary, reactions were performed
under an inert atmosphere. Semi-preparative HPLC separations
were carried out using a 10 ꢁ 250 mm2 i.d. Daicel Chiral Pak 1A
HO2C
OH
O
TMSEO2C
OH
O
N
HO
HO
N
H
TASF
H
O
DMF, 40ꢁC
1 h, 15 %
O
H
O
H
O
O
O
63
64
Scheme 13.
as that observed for platencin, namely that they were only
weakly active materials (. 16 mg mLꢀ1). In contrast, platencin
inhibited the growth of S. aureus and H. influenzae at 4 mg mLꢀ1
but analogues 58, 61, and 64 proved ineffective against all four
of these same pathogens as revealed by their anti-bacterial
activities being above 16 mg mLꢀ1. These biological data are
summarised in Table 1.
Conclusion
The work detailed above has provided the capacity to generate a
range of analogues of the tricarbocyclic core of platencin. While
previous studies have established that modest variations in this
core allow for the retention of anti-bacterial activity,[2b] the
incorporation of an acetonide residue into such a framework (as
seen in compounds 58, 61, and 64) at the expense of the exo-
cyclic double bond (as seen in the natural product) clearly has
adverse impacts. Nevertheless, other opportunities for varia-
tions within this framework are likely to be available through the
transformations reported here and these are now being pursued.
The outcomes of such studies will be reported in due course.
Table 1. Comparison of the anti-bacterial properties of compounds 58, 61, and 64 with a naturally derived sample of platencin and with
chloramphenicol
CompoundA
Minimal inhibitory concentrationB [mg mLꢀ1
]
Streptococcus pynogens
Staphylococcus aureus
Enterococcus faecium
Haemophilus influenzae
ATCC 51339
ATCC 19636
ATCC 19434
ATCC 49247
58
.16
.16
.16
4
.16
.16
.16
.16
#2.0
.16
.16
.16
4
.16
.16
.16
.16
#2.0
61
64
Platencin (1)
Chloroamphenicol
#2.0
#2.0
ACompounds were tested in doubling dilutions over the concentration range 0.008–16 mg mLꢀ1
.
BThe minimal inhibitory concentration is the lowest compound concentration needed to inhibit visible bacterial growth or to inhibit growth based on
absorbance readings.

Chemoenzymatic Syntheses of Some Analogues of Platencin
I
column packed with amylose tris(3,5-dimethylphenyl carba-
mate) immobilised on 5 mm silica gel. An eluting solvent of
9 : 90 : 1 v/v/v iso-propyl alcohol/hexane/TFA was used at a
dark-coloured reaction mixture was diluted with diethyl ether
(25 mL) and Na2S2O3 (7.5 mL of a 10 % w/v aqueous solution).
The separated aqueous phase was extracted with diethyl ether
(3 ꢁ 25 mL) and the combined organic fractions were washed
with brine (1 ꢁ 15 mL) before being dried (Na2SO4), filtered,
and concentrated under reduced pressure to give a clear, light-
yellow oil. Subjection of this material to flash column chroma-
tography (silica, 1 : 9 v/v ethyl acetate/hexane elution) and
concentration of appropriate fractions (Rf 0.5), afforded iodide
18 (140 mg, 79 %) as a clear, colourless oil. dH (400 MHz,
CDCl3) 5.79 (m, 1H), 5.06 (m, 1H), 5.02 (s, 1H), 3.74 (m, 1H),
3.18 (t, J 7.0, 2H), 2.21 (m, 2H), 1.99–1.76 (complex m, 2H),
1.63–1.44 (complex m, 2H), 0.88 (s, 9H), 0.05 (s, 6H). dC
(101 MHz, CDCl3) 134.9, 117.2, 71.1, 42.0, 37.5, 29.6, 26.0,
18.2, 7.4, ꢀ4.2, ꢀ4.4. nmax (KBr)/cmꢀ1 2955, 2928, 2850, 1641,
1471, 1462, 1436, 1361, 1255, 1071 1004, 913, 835, 774, 719. m/
z (ESI, þve) 377 ([M þ Na]þ, 100 %). HRMS m/z 377.0774;
C13H27IOSi [M þ H]þ requires 377.0774.
flow rate of 4.5 mL minꢀ1
.
Specific Synthetic Transformations
Compound 16
A magnetically stirred solution of commercially available
hepta-1,6-dien-4-ol (13.45 g, 0.12 mol) in dry CH3CN (50 mL)
maintained under nitrogen atmosphere at 228C was treated with
t-butyldimethylsilyl chloride (TBDMS-Cl) (19.6 g, 0.13 mol)
and the resulting mixture stirred for a further 0.25 h before being
treated, in portions, with imidazole (250 mg, 1.0 mmol). The
reaction mixture thus obtained was left to stir for 16 h before
being diluted with hexane (90 mL), washed with water
(1 ꢁ 35 mL) and brine (1 ꢁ 35 mL), dried (Na2SO4), filtered,
and concentrated under reduced pressure. The resulting viscous
light-yellow oil was subjected to flash column chromatography
(silica, 1 : 9 v/v ethyl acetate/hexane elution) to afford, after
concentration of the relevant fractions (Rf 0.8 in 3 : 7 v/v ethyl
acetate/hexane), compound 16 (24.7 g, 91 %) as a clear, colour-
less oil. dH (400 MHz, CDCl3) 5.90–5.74 (complex m, 2H), 5.05
(m, 2H), 5.02 (s, 2H), 3.75 (p, J 5.9, 1H), 2.33–2.10 (complex m,
4H), 0.89 (s, 9H), 0.05 (s, 6H). These data matched those
reported previously.[5]
Compound 19
A magnetically stirred solution of iodide 18 (179 mg,
0.50 mmol) in diethyl ether (5 mL) maintained under a nitrogen
atmosphere at ꢀ788C was treated dropwise with t-BuLi (617 mL
of a 1.7 M solution in pentane, 1.05 mmol) over 3 min and then
stirred at this temperature for a further 5 min After this time a
solution of anhydrous ZnI2 (175 mg, 0.55 mmol) in dry THF
(750 mL) was added to the reaction mixture and stirring contin-
ued for a further 10 min before it was warmed to 228C over 1 h.
At this point, a solution of freshly prepared iodide 4 (140 mg,
0.5 mmol) and Pd(PPh3)4 (9 mg, 0.08 mmol) in THF (750 mL)
was added, dropwise, and stirring continued for 2 h. After this
time the reaction mixture was quenched with NaHCO3 (10 mL
of a saturated aqueous solution) and the separated aqueous phase
extracted with diethyl ether (3 ꢁ 15 mL). The combined organic
phases were washed with brine (1 ꢁ 15 mL), dried (Na2SO4),
filtered, and concentrated under reduced pressure to give a clear,
light-yellow oil. This was subjected to flash column chromatog-
raphy (1 : 99 to 1 : 19 v/v ethyl acetate/hexane gradient elution)
to afford, after concentration of the relevant fractions (Rf 0.4 in
1 : 4 v/v ethyl acetate/hexane), a ,1 : 1 mixture of the diastereo-
isomeric forms of compound 19 (123 mg, 65 %) as a clear,
colourless oil. dH (400 MHz, CDCl3) 5.98 (m, 1H), 5.84–5.75
(complex m, 2H), 5.72 (m, 1H), 5.05 (m, 2H), 4.64 (m, 1H), 4.52
(dd, J 8.7 and 2.5, 1H), 3.71 (m, 1H), 2.27–2.18 (complex m,
4H), 1.43–144 (complex m, 4H), 1.41 (s, 3H), 1.39 (s, 3H), 0.89
(s, 9H), 0.05 (br s, 6H). dC (101 MHz, CDCl3) 138.5, 135.9,
135.5, 128.4, 125.7, 124.9, 124.8, 122.7, 118.4, 116.8, 105.4,
86.1, 73.5, 71.9, 71.5, 42.2, 42.1, 36.6, 34.4, 33.8, 30.5, 27.1,
26.1, 25.2, 23.0(4), 22.9(7), 21.3, 18.3, ꢀ4.21, ꢀ4.4 (ten
resonances obscured or overlapping). nmax (KBr)/cmꢀ1 3047,
2986, 2933, 2891, 1644, 1570, 1454, 1394, 1379, 1371, 1302,
1233, 1210, 1157, 1060, 1033, 982, 869, 787, 723, 622. m/z (ESI,
þve) 401 ([M þ Na]þ, 20 %), 147 (100). HRMS m/z 401.2487;
C22H38O3Si [M þ H]þ requires 401.2488.
Compound 17
A magnetically stirred solution of diene 16[5] (226 mg,
1.0 mmol) in dry THF (19.0 mL) maintained at 228C under an
atmosphere of nitrogen was treated, via syringe, with 9-borabi-
cyclo[3.3.1]nonane (2.56 mL of a 0.43 M solution in THF,
1.1 mmol). The ensuing mixture was stirred for 1 h and then
treated with water (7.5 mL) and NaBO3ꢂ4H2O (5 equiv.)
(CAUTION: exothermic reaction). The ensuing heterogeneous
mixture was stirred vigorously for an additional 1 h and then
treated with NH4Cl (10 mL of a saturated aq. solution) before
being extracted with ethyl acetate (3 ꢁ 15 mL). The combined
organic extracts were washed with brine (1 ꢁ 10 mL), dried
(MgSO4), filtered, and concentrated under reduced pressure to
give a clear, light-yellow oil. Subjection of this material to flash
column chromatography (silica, 1 : 9 v/v ethyl acetate/hexane
elution) afforded, after concentration of the relevant fractions
(Rf 0.5 in 1 : 4 v/v ethyl acetate/hexane), the title alcohol 17[10]
(183 mg, 75 %) as a clear, colourless liquid. dH (400 MHz,
CDCl3) 5.78 (m, 1H), 5.08–5.00 (complex m, 2H), 3.79 (m, 1H),
3.62 (m, 2H), 2.25 (m, 2H), 1.98 (br. s, 1H), 1.69–1.50 (complex
m, 4H), 0.89 (s, 9H), 0.06 (s, 6H). dC (101 MHz, CDCl3) 135.2,
117.1, 71.9, 63.3, 41.7, 33.2, 28.4, 26.0, 18.3, ꢀ4.3, ꢀ4.4. nmax
(KBr)/cmꢀ1 3352, 3077, 2955, 2930, 2887, 2858, 1641, 1472,
1463, 1434, 1412, 1388, 1361, 1328, 1255, 1187, 1071, 1028,
1005, 969, 938, 912, 869, 836, 775, 665. m/z (ESI, þve) 267
([M þ Na)þ, 20 %), 70 (100). HRMS m/z 267.1756; C13H28O2Si
[M þ H]þ requires 267.1756.
Compound 18
Compound 20
A magnetically stirred solution of alcohol 17 (122 mg,
0.5 mmol) in anhydrous diethyl ether (10 mL) maintained under
an atmosphere of nitrogen was cooled to 08C and then treated
with imidazole (72 mg, 1.05 mmol), triphenylphosphine
(262 mg, 1.0 mmol), and molecular iodine (255 mg, 1.05 mmol).
The ensuing mixture was allowed to warm to 228C and stirred
at this temperature for a further 2 h. After this time, the now
A magnetically stirred solution of silyl ether 19 (135 mg,
0.357 mmol) in THF (7.5 mL) maintained at 08C was treated
with TBAF (750 mL of a 1.0 M solution in THF, 0.75 mmol).
Stirring was continued for 0.25 h and then the reaction mixture
was warmed to 228C and stirring continued for further for 8 h at
this temperature. After this time the reaction mixture was

J
R. N. Muhammad et al.
concentrated under reduced pressure and the residue thus
obtained subjected to flash column chromatography (silica,
3 : 7 v/v ethyl acetate/hexane elution) to afford, after concentra-
tion of the relevant fractions (Rf 0.3 in 1 : 1 v/v ethyl acetate/
hexane), a ,1 : 1 mixture of the diastereoisomeric forms of
compound 20 (47.6 mg, 51 %) as a clear, colourless oil. dC
(101 MHz, CDCl3) 143.5, 140.2, 139.1, 133.6, 128.9, 125.3,
124.7, 109.4, 108.8, 106.0, 104.0, 101.5, 84.9, 79.2, 78.7, 77.9,
75.4, 71.7, 48.4, 45.7, 38.5, 35.4, 28.0, 26.9, 26.8, 25.6, 25.3
(five resonances obscured or overlapping). nmax (KBr)/cmꢀ1
3415, 3047, 2983, 2932, 1640, 1443, 1375, 1370, 1259, 1210,
1158, 1046, 914, 884, 747, 667. m/z (EI, 70 eV) 264 (Mþꢃ, , 1
%), 263 ([M – Hꢃ]þ, 3), 249 ([M – CH3ꢃ]þ, 100). HRMS m/z
264.1726; C16H24O3 Mþꢃ requires 264.1725.
([M – CH3ꢃ]þ, 100), 192 (85), 157 (66), 148 (93), 130 (88), 105
(80), 91 (75). HRMS m/z 250.1568; C15H22O3 Mþꢃ requires
250.1569.
Compound 26
A magnetically stirred solution of allylic alcohol 25 (1.14 g,
4.5 mmol) in dry toluene (21 mL) maintained under an argon
atmosphere and protected from light was cooled to 08C before
being treated, dropwise over 0.5 h, with diethyl zinc (13.5 mL
of a 1 M solution in hexane, 13.5 mmol) and diiodomethane
(1.01 mL, 13.1 mmol). After 0.5 h the reaction mixture was
allowed to warm to 228C and stirred at this temperature for
1.5 h. NH4Cl (40 mL of a saturated aqueous solution) was then
carefully added to the reaction mixture which was then
extracted with dichloromethane (5 ꢁ 25 mL). The combined
organic phases were washed successively with NaHCO3
(1 ꢁ 15 mL of a saturated aqueous solution) and water
(1 ꢁ 15 mL) before being dried (Na2SO4), filtered, and con-
centrated under reduced pressure. The residue thus obtained
was subjected to flash column chromatography (silica, 3 : 7 v/v
ethyl acetate/hexane elution) to afford, after concentration of
the appropriate fractions (Rf 0.25 in 1 : 4 v/v ethyl acetate/
hexane), compound 26 (920 mg, 77 %) as a white, crystalline
solid, mp 146–1488C, [a]D ꢀ63.1 (c 1.0, CHCl3). dH (400 MHz,
CDCl3) 4.17–4.08 (complex m, 2H), 3.99 (dd, J 8.0 and 1.3,
1H), 1.80 (m, 1H), 1.73–1.53 (complex m, 6H), 1.57 (s, 3H),
1.37 (s, 3H), 1.31–0.97 (complex m, 6H), 0.41 (td, J 8.9 and
5.3, 1H), 0.32 (q, J 5.5, 1H). dC (101 MHz, CDCl3) 108.5, 82.2,
76.2, 69.1, 35.1, 32.0, 31.5, 30.3, 29.3, 26.1, 24.4, 22.1, 19.9,
19.7, 18.6, 3.1. nmax (KBr)/cmꢀ1 3402, 2987, 2930, 2865, 1469,
1380, 1371, 1283, 1259, 1207, 1164, 1143, 1098, 1085, 1065,
1031, 1009, 911, 876, 732. m/z (EI, 70 eV) 249 ([M – CH3ꢃ]þ,
100 %). HRMS m/z 249.1498; C16H24O3 [M – CH3ꢃ]þ requires
249.1491.
Attempted Nucleophilic Cyclopropanation of Enone 23
A magnetically stirred suspension of sodium hydride
(40 mg, 1.01 mmol) in DMSO (1.0 mL) was treated with
trimethylsulfoxonium iodide (334 mg, 1.52 mmol) and the
ensuing mixture stirred at 228C for 0.5 h. A solution of enone
23[9] (24.8 mg, 0.10 mol) in DMSO (1.0 mL) was then added to
the reaction mixture that was then stirred for a further 2.5 h.
After this time the reaction temperature was raised to 508C and
stirring continued at this temperature for 0.5 h. The cooled
reaction mixture was then treated with diethyl ether (5 mL)
followed by pH 7 aqueous buffer (5 mL). The separated
aqueous phase was extracted with diethyl ether (5 ꢁ 10 mL)
and the combined organic phases were dried (MgSO4), filtered,
and concentrated under reduced pressure to give a clear,
light-yellow oil (21 mg). NMR spectroscopic and TLC
analyses of this material suggested it was a mixture of products.
1
The presence of olefinic proton resonances in the H NMR
spectrum of the crude reaction mixture and the absence of a
carbonyl absorption band in the infrared spectrum of this
material suggested that spiro-epoxidation (leading, at least in
part, to compound 24), rather than nucleophilic cyclopropana-
tion, had taken place.
Compound 27
A magnetically stirred solution of alcohol 26 (501 mg,
1.90 mmol)) and DMP (481 mg, 2.85 mmol) in dry dichlor-
omethane (25.0 mL) was stirred at 228C for 0.25 h and then
concentrated under reduced pressure. The residue thus obtained
was redissolved in a minimum volume of diethyl ether and the
resulting solution washed with Na2S2O3/NaHCO3 (1 ꢁ 35 mL
of a 1 : 1 v/v mixture of 10 % w/v solution and a saturated
aqueous solution, respectively), water (1 ꢁ 20 mL), and brine
(1 ꢁ 20 mL). The combined aqueous washings were extracted
with diethyl ether (1 ꢁ 40 mL) and the combined organic layers
then dried (Na2SO4), filtered, and concentrated under reduced
pressure. Subjection of the residue thus obtained to flash column
chromatography (silica, 1 : 4 v/v ethyl acetate/hexane elution)
afforded, after concentration of the appropriate fractions (Rf
0.4), ketone 27 (474 mg, 95 %) as a white, crystalline solid, mp
151–154, [a]D ꢀ51.7 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 4.26
(m, 1H), 4.07 (m, 1H), 2.21 (t, J 13.8, 1H), 2.00 (m, 1H), 1.93–
1.61 (complex m, 7H), 1.53 (s, 3H), 1.36 (s, 3H), 1.30–1.09
(complex m, 3H), 1.06 (m, 1H), 0.95 (m, 1H). dC (101 MHz,
CDCl3) 209.5, 108.7, 81.6, 76.0, 40.0, 38.6, 32.3, 30.4, 29.7,
28.7, 26.0, 25.5, 24.4, 19.7, 19.5, 13.5. nmax (KBr)/cmꢀ1 2993,
2985, 2954, 2896, 1693, 1453, 1380, 1372, 1271, 1256, 1209,
1130, 1068, 1038, 1025, 994, 948, 910, 862, 805, 778, 733, 644,
516. m/z (ESI, þve) 317 (73 %), 301 (100), 285 ([M þ Na]þ, 50),
263 (18). HRMS m/z 285.1467; C16H22O3 [M þ H]þ requires
285.1467.
Compound 25
A magnetically stirred solution of enone 23 (1.24 g,
5.0 mmol) and CeCl3ꢂ7H2O (3.71 g, 10.0 mmol) in methanol
(19 mL) was cooled to 08C and then treated, in portions over
0.5 h, with NaBH4 (375 mg, 10.0 mmol). The ensuing mixture
was allowed to warm to 228C and then stirred at this temperature
for a further 2.5 h before water (10 mL) was slowly added. After
hydrogen gas evolution had ceased the reaction mixture was
concentrated under reduced pressure and the residue thus
obtained extracted with dichloromethane (5 ꢁ 15 mL). The
combined organic phases were then dried (Na2SO4), filtered,
and concentrated under reduced pressure to give a white,
crystalline solid. Recrystallisation (hexane/methanol) of this
material gave alcohol 25 (1.09 g, 87 %) as a white solid, mp
108–1168C, [a]D ꢀ31.2 (c 1.0, CHCl3) (Rf 0.3 in 3 : 7 v/v ethyl
acetate/hexane). dH (400 MHz, CDCl3) 5.69 (dd, J 10.1 and 2.0,
1H), 5.58 (m, 1H), 4.23 (m, 1H), 4.12 (m, 1H), 3.71 (dd, J 8.1 and
1.4, 1H), 2.04 (m, 1H), 1.88–1.74 (complex m, 3H), 1.70–1.59
(complex m, 2H), 1.52 (s, 3H), 1.47 (m, 1H), 1.33 (s, 4H), 1.30
(m, 1H), 1.26–1.14 (complex m, 2H). dC (101 MHz, CDCl3)
134.0, 130.8, 108.7, 79.4, 75.9, 68.1, 36.3, 35.3, 31.8, 30.0, 29.9,
26.0, 24.4, 20.9, 19.5. nmax (KBr)/cmꢀ1 3407, 2987, 2932, 2868,
1463, 1373, 1277, 1260, 1207, 1163, 1063, 1013, 994, 968, 931,
894, 876, 732, 647, 522. m/z (EI, 70 eV) 250 (Mþꢃ, 18 %), 235

Chemoenzymatic Syntheses of Some Analogues of Platencin
K
Compound 28
before being warmed to 228C and treated, dropwise via syringe,
with acetic acid (90 mg, 1.50 mmol). The ensuing mixture was
stirred for a further 1.5 h at this temperature and then diluted
with dichloromethane (15 mL) and quenched (CAUTION:
exothermic reaction with accompanying gas evolution) with
NaHCO3 (10 mL of a saturated aqueous solution). The ensuing
mixture was extracted with dichloromethane (4 ꢁ 15 mL) and
the combined organic phases washed with brine (1 ꢁ 20 mL),
dried (MgSO4), filtered, and concentrated under reduced pres-
sure. The residue thus obtained was subjected to flash column
chromatography (silica, 1 : 9 v/v ethyl acetate/hexanes elution)
to afford, after concentration of the relevant fractions (Rf 0.5 in
1 : 1 v/v ethyl acetate/hexane), compound 30 (71 mg, 71 %) as a
white, crystalline solid, mp 95–968C, [a]D þ37.2 (c 1.0, CHCl3).
dH (400 MHz, CDCl3) 5.87 (m, 1H), 5.78 (m, 1H), 4.24 (dd, J 8.4
and 1.9, 1H), 4.18 (m, 1H), 3.67 (dd, J 4.9 and 1.4, 1H), 2.28 (m,
1H), 1.94–1.83 (complex m, 4H), 1.68 (m, 2H), 1.54 (s, 3H),
1.45 (m, 1H), 1.39 (s, 3H), 1.35–1.15 (complex m, 3H). dC
(101 MHz, CDCl3) 131.3, 127.2, 108.5, 76.0, 75.8, 67.8, 37.8,
32.6, 30.6, 28.6, 26.0, 25.5, 24.5, 19.3, 17.2. nmax (KBr)/cmꢀ1
3399, 2925, 2862, 1469, 1380, 1259, 1207, 1164, 1064, 1031,
876, 807, 518. m/z (EI, 70 eV) 250 (Mþꢃ, 5 %), 235
([M – CH3ꢃ]þ, 85), 149 (100). HRMS m/z 250.1562;
C15H22O3 Mþꢃ requires 250.1569.
A magnetically stirred solution of compound 27 (263 mg,
1.00 mmol) in dry THF/HMPA (10 mL of a 3 : 1 v/v mixture)
and maintained under nitrogen at ꢀ788C was treated, dropwise,
with KHMDS (2.5 mL of a 0.5 M solution in toluene,
1.25 mmol). The ensuing mixture was stirred at ꢀ788C for
0.5 h then treated, dropwise, with iodomethane (449 mL of
material freshly filtered through anhydrous K2CO3, 7.00 mmol).
The ensuing mixture was stirred for 0.5 h and then allowed to
warm to 08C over a period of 1 h before being treated with
NaHCO3 (10 mL of a saturated aqueous solution) and extracted
with dichloromethane (4 ꢁ 15 mL). The combined organic
extracts were washed with brine (1 ꢁ 10 mL), dried (Na2SO4),
filtered, and concentrated under reduced pressure. The residue
thus obtained was subjected to flash column chromatography
(silica, 1 : 4 v/v ethyl acetate/hexane elution) to afford, after
concentration of the appropriate fractions (Rf 0.5), compound 28
(197 mg, 75 %) as a white, crystalline solid, mp 176–182, [a]D
ꢀ32.1 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 4.15 (m, 1H), 4.07
(dd, J 7.9 and 1.4, 1H), 2.20 (m, 1H), 1.97–1.58 (complex m,
7H), 1.54 (s, 3H), 1.37 (s, 3H), 1.32–1.21 (complex m, 3H), 1.05
(m, 1H), 0.98 (t, J 3.3, 1H), 0.95 (d, J 6.6, 3H). dC (101 MHz,
CDCl3) 211.2, 108.9, 81.6, 75.8, 46.0, 38.7, 32.7, 30.5, 28.7,
28.4, 26.0, 25.5, 24.4, 20.4, 19.7, 13.8, 10.8. nmax (KBr)/cmꢀ1
2985, 2937, 2897, 1688, 1456, 1374, 1354, 1285, 1257, 1208,
1161, 1130, 1086, 1064, 1044, 970, 935, 876, 829, 807, 738, 640,
509. m/z (ESI, þve) 331 (100 %), 299 ([M þ Na]þ, 48), 277 (15).
HRMS m/z 299.1623; C17H24O3 [M þ H]þ requires 299.1623.
Compound 14
A magnetically stirred solution of allylic alcohol 30 (71 mg,
0.28 mmol) in anhydrous dichloromethane (7.0 mL) maintained
at 228C under a nitrogen atmosphere was treated with molecular
Compound 29
˚
sieves (75 mg of powered, anhydrous 4 A material), pyridinium
A magnetically stirred solution of enone 23 (150 mg,
0.60 mmol) in methanol (25 mL) was cooled to 08C and then
treated, successively, with hydrogen peroxide (217 mL of a 35%
w/v aqueous solution, 2.1 mmol) and sodium hydroxide (109 mL
of 6 M aqueous solution, 0.65 mmol). The ensuing mixture was
warmed to 228C, stirred at this temperature for 1.5 h and then
poured into a mixture of ethyl acetate (25 mL) and NH4Cl (20 mL
of a saturated aqueous solution). The separated aqueous layer was
extracted with ethyl acetate (4 ꢁ 15 mL) and the combined
organic phases were then dried (Na2SO4), filtered, and concen-
trated under reduced pressure. The light-yellow residue thus
obtained was subjected to flash column chromatography (silica,
3 : 7 : 0.1 v/v/v ethyl acetate/hexane/acetic acid elution) to afford,
after concentration of the appropriate fractions (Rf 0.5 in 3 : 7 : 0.1
v/v/v ethyl acetate/hexane/acetic acid) compound 29 (127 mg,
79 %) as a white, crystalline solid mp 79–808C, [a]D þ9.45 (c 1.0,
CHCl3). dH (400 MHz, CDCl3) 4.21–4.11 (complex m, 2H), 3.43
(d, J 3.9, 1H), 3.25 (d, J 3.9, 1H), 2.61 (m, 1H), 2.08 (m, 1H),
2.00–1.08 (complex m, 6H), 1.54 (s, 3H), 1.39 (s, 3H), 1.20 (m,
1H), 1.05 (m, 1H). dC (101 MHz, CDCl3) 204.7, 109.1, 75.4, 59.1,
55.1, 41.8, 35.1, 31.1, 29.4, 25.9, 25.0, 24.3, 18.2, 16.2 (one
resonance obscured or overlapping). nmax (KBr)/cmꢀ1 2935,
2925, 1710, 1467, 1406, 1380, 1260, 1207, 1163, 1115, 1067,
1031, 982, 918, 877, 854, 822, 803. m/z (EI, 70 eV) 249
([M – CH3ꢃ]þ, 100 %). HRMS m/z 249.1130; C15H20O4
[M – CH3ꢃ]þ requires 249.1127.
dichromate (PDC 117 mg, 0.31 mmol), and then acetic acid
(95 mL, 16.6 mmol). The resulting mixture was stirred at 228C
for 1.5 h and then treated with Celite (1.50 g) before being
filtered through a sintered-glass funnel. The filtrate thus
obtained was concentrated under reduced pressure and the
ensuing residue subjected to flash column chromatography
(silica, 1 : 4 v/v ethyl acetate/hexane elution) to afford, after
concentration of the appropriate fractions (Rf 0.5 in 3 : 7 v/v
ethyl acetate/hexane), enone 14 (67 mg, 97 %) as a white,
crystalline solid, mp 104–1078C, [a]D þ 59.05 (c 1.0, CHCl3).
dH (800 MHz, CDCl3) 6.83 (ddd, J 10.2, 5.8, and 2.2, 1H), 5.94
(m, 1H), 4.15 (dd, J 8.1 and 1.7, 1H), 4.10 (ddd, J 8.1, 3.3 and
1.4, 1H), 2.55 (m, 1H), 2.32 (m, 1H), 1.96 (m, 2H), 1.87–1.78
(complex m, 3H), 1.58 (s, 3H), 1.42 (s, 3H), 1.35–1.20 (complex
m, 3H). dC (201 MHz, CDCl3) 202.6, 147.6, 129.5, 108.9, 76.1,
76.0, 46.0, 32.5, 30.5, 29.9, 28.8, 26.2, 24.3, 18.9, 17.0. nmax
(KBr)/cmꢀ1 2923, 2852, 1737, 1673, 1465, 1379, 1263, 1207,
1166, 1121, 1074, 1015, 963, 918, 879, 797, 745, 646. m/z (EI,
70 eV) 248 (Mþꢃ, 22 %), 233 ([M – CH3ꢃ]þ, 100). HRMS m/z
233.1179; C15H20O3 [M – CH3ꢃ]þ requires 233.1178.
Compound 31
A magnetically stirred slurry of dry copper(I) iodide (389 mg,
2.0 mmol) in distilled diethyl ether (17 mL) maintained at ꢀ788C
under nitrogen was treated, dropwise, with methyl lithium
(2.5 mL of a 1.6 M solution in diethyl ether, 4.0 mmol). The
resulting light-tan coloured solution was stirred for 0.33 h at this
temperature and then a solution of the enone 23 (248 mg,
1.0 mmol) in diethyl ether (3.5 mL) was added, via syringe pump,
over 0.17 h. The ensuing bright-yellow reaction mixture was
stirred for 1 h at ꢀ788C and then quenched with NH4Cl solution
(15 mL of a saturated aqueous solution). The separated aqueous
Compound 30
A magnetically stirred solution of epoxy-ketone 29 (105 mg,
0.4 mmol) in anhydrous methanol (5 mL) was cooled to 08C and
then treated, dropwise, with hydrazine hydrate (75 mg,
1.50 mmol). The ensuing mixture was stirred at 08C for 0.5 h

L
R. N. Muhammad et al.
layer was extracted with diethyl ether (3ꢁ 25 mL) and the
combined organic phases washed with brine (1ꢁ 10 mL) before
being dried (Na2SO4), filtered, and concentrated under reduced
pressure to give a clear, light-yellow oil. Subjection of this oil to
flash column chromatography (silica, 3 : 7 v/v ethyl acetate/
hexane elution) and concentration of the relevant fractions (Rf
0.5) afforded compound 31 (187 mg, 71 %) as a white, crystalline
solid, mp 147–1548C, [a]D þ19.5 (c 1.0, CHCl3). dH (400 MHz,
CDCl3) 4.13 (ddd, J 8.4, 3.8, and 1.3, 1H), 3.98 (dd, J 8.4 and 2.0,
1H), 2.67 (dd, J 14.3 and 6.2, 1H), 2.42–2.26 (complex m, 2H),
2.12–1.59 (complex m, 9H), 1.51 (s, 3H), 1.35 (s, 3H), 1.14 (m,
1H), 0.94 (d, J 7.3, 3H). dC (101 MHz, CDCl3) 211.5, 108.4, 76.7,
75.7, 46.2, 45.0, 36.3, 36.2, 31.1, 31.0, 28.8, 25.9, 24.3, 19.3, 19.1,
15.8. nmax (KBr)/cmꢀ1 2998, 2973, 2960, 2925, 2863, 1705, 1466,
1454, 1430, 1417, 1382, 1374, 1288, 1266, 1203, 1145, 1080,
1064, 1025, 993, 972, 939, 908, 878, 832, 733, 671, 648, 601, 515.
m/z (EI, 70 eV) 249 ([M – CH3ꢃ]þ, 100 %). HRMS m/z 249.1491;
C16H24O3 [M – CH3ꢃ]þ requires 249.1491.
(187.6 mg, 0.75 mmol) in dichloromethane (10 mL) main-
tained at 228C was treated, in portions, with DMP (353 mg,
0.83 mmol). The ensuing mixture was stirred for 2.5 h before
being diluted with dichloromethane (10 mL) and the resulting
solution washed with Na2S2O3 (1 ꢁ 15 mL of a saturated
aqueous solution) and NaHCO3 (1 ꢁ 15 mL of a saturated
aqueous solution). The combined aqueous phases were
extracted with dichloromethane (3 ꢁ 15 mL) and the combined
organic phases were washed with brine (1 ꢁ 15 mL) then dried
(Na2SO4), filtered, and concentrated under reduced pressure to
give a clear, colourless oil. Subjection of this material to flash
column chromatography (silica, 3 : 7 v/v ethyl acetate/hexane
elution) and concentration of appropriate fractions (Rf 0.4)
afforded compound 33 (140 mg, 75 %) as a white, crystalline
solid, mp 122–1248C, [a]D þ42.5 (c 1.0, CDCl3). dH (400 MHz,
CDCl3) 6.26 (m, 1H), 6.04 (m, 1H), 4.20 (m, 1H), 3.77 (m, 1H),
2.82 (br s, 1H), 2.52–2.28 (complex m, 3H), 2.19 (m, 1H), 1.99
(m, 1H), 1.77–1.60 (complex m, 3H), 1.31 (s, 3H), 1.25 (s, 3H),
0.85 (m, 1H). dC (101 MHz, CDCl3) 211.1, 132.4, 130.9, 108.8,
83.5, 79.3, 47.1, 41.7, 38.1, 36.7, 34.7, 31.9, 29.6, 25.6, 25.1.
nmax (KBr)/cmꢀ1 2986, 2938, 2869, 1714, 1455, 1431, 1379,
1366, 1266, 1245, 1206, 1110, 1165, 1065, 1042, 1009, 986,
954, 879, 841, 726, 699, 525, 514. m/z (ESI, þve) 303 (98 %),
271 ([M þ Na]þ, 100). HRMS m/z 271.1312; C15H2O3
[M þ H]þ requires 271.1310.
Compounds 15 and 32
Step i. A magnetically stirred solution of ketone 31
(157 mg, 0.59 mmol) in dry dichloromethane (7.5 mL) main-
tained under an atmosphere of nitrogen was cooled to 08C then
treated with trimethylamine (660 mL, 7.1 mmol) and TMSOTf
(600 mL, 3.54 mmol). The resulting mixture was stirred at 08C
for 1.5 h, after which time it was warmed to 228C and stirred for
a further 0.5 h before being diluted with hexane (65 mL).
The resulting solution was washed with NaHCO3 (1 ꢁ 15 mL
of a saturated aqueous solution) and brine (1 ꢁ 10 mL), dried
(MgSO4) then filtered, and concentrated under reduced pressure
to give a clear, colourless oil that is presumed to be comprising
of the anticipated mixture of silyl enol ethers.
Step ii. The oil obtained from step i was dissolved in DMSO
(500 mL) and the resulting solution treated with IBX (2.21 mL of
a 0.4 M solution in DMSO, 0.89 mmol) and MPO (2.21 mL of a
0.4 M solution in DMSO, 0.89 mmol). The ensuing mixture
was stirred at 228C for 16 h while being protected from light and
then quenched with NaHCO3 (7.5 mL of a saturated aqueous
solution) before being extracted with ethyl acetate (4 ꢁ 10 mL).
The combined organic extracts were washed with brine
(1ꢁ 10 mL), dried(MgSO4) then filtered, and concentrated under
reduced pressure to give a clear, light-yellow oil. Subjection of
this material to flash column chromatography (silica, 1 : 9 v/v
ethyl acetate/hexane elution) gave, after concentration of the
relevant fractions (Rf 0.5 in 2 : 8 v/v ethyl acetate/hexane), a
,2 : 3 mixture of enones 15 and 32 (122 mg, 79 % combined
yield) as a white, crystalline and chromatographically inseparable
solid, mp 80–1168C. dH (400 MHz, CDCl3) 5.93 (m, 2/5H), 5.80
(br s, 3/5H), 4.15–4.10 (complex m, 1H), 3.90 (m, 3/5H), 3.48 (br
s, 2/5H), 2.55–2.20(complexm, 4H), 2.10(m, 1H), 2.02(s, 1.8H),
2.00–1.75 (complex m, 4H), 1.57 (s, 4.2H), 1.50–1.15 (complex
m, 3.8H), 1.08 (d, J 8.0, 1.2H). dC (101 MHz, CDCl3) 198.8,
198.6, 167.4, 165.5, 127.6, 126.4, 109.4, 108.6, 78.1, 76.0, 75.9,
73.0, 42.3, 41.7, 40.9, 40.6, 35.1, 33.4, 32.6, 31.0, 30.5, 29.4, 26.2,
26.1, 24.5, 24.4, 22.7, 22.3, 19.1, 18.3, 16.8 (one resonance
obscured or overlapping). nmax (KBr)/cmꢀ1 2939, 2882, 1713,
1675, 1372, 1259, 1203, 1063, 875, 514. m/z (EI, 70 eV) 262
(Mþꢃ, 60), 247 (45), 85 (95), 83 (92), 51 (100). HRMS m/z
262.1565; C16H22O3 Mþꢃ requires 262.1569.
Compounds 34 and 35
A magnetically stirred solution of ketone 33 (248 mg,
1.0 mmol) in dry dichloromethane (13.0 mL) maintained under
an atmosphere of nitrogen was cooled to 08C then treated
with trimethylamine (975 mL, 10.5 mmol) and TMSOTf
(1.03 mL, 6.0 mmol). The mixture thus obtained was stirred at
08C for 1 h then warmed to 228C and stirred at this temperature
for a further 0.5 h before being diluted with hexane (125 mL),
washed with NaHCO3 (1 ꢁ 25 mL of a saturated aqueous
solution) and brine (1 ꢁ 15 mL), dried (Na2SO4), filtered, and
concentrated under reduced pressure to give a clear, light-
yellow oil. This oil was dissolved in DMSO (1.0 mL) and the
resulting solution treated with a solution of IBX (3.95 mL of
0.4 M solution in DMSO, 1.58 mmol) and MPO (3.95 mL of
0.4 M solution in DMSO, 1.58 mmol) then stirred at 228C for
16 h while being protected from light. After this time the
reaction mixture was quenched with NaHCO3 (15 mL of a
saturated aqueous solution) and extracted with ethyl acetate
(5 ꢁ 15 mL). The combined organic extracts were washed with
brine (1 ꢁ 25 mL) before being dried (Na2SO4), filtered, and
concentrated under reduced pressure to give a clear, light-
yellow oil. Subjection of this oil to flash column chromatogra-
phy (silica 1 : 9 v/v ethyl acetate/hexane elution) afforded two
fractions, A and B.
Concentration of fraction A (Rf 0.3(7) in 3 : 7 v/v ethyl
acetate/hexane) afforded compound 34 (54 mg, 21 %) as a
white, crystalline solid, mp 146–1488C, [a]D þ10.7 (c 1.0,
CHCl3). dH (400 MHz, CDCl3) 6.31 (t, J 7.2, 1H), 5.96 (d, J
2.0, 1H), 5.83 (d, J 7.2, 1H), 4.33 (m, 1H), 4.19 (dd, J 7.2 and 1.3,
1H), 3.07 (m, 1H), 2.53–2.22 (complex m, 6H), 1.35 (s, 3H),
1.29 (s, 3H). dC (101 MHz, CDCl3) 197.9, 162.3, 133.2, 132.2,
125.9, 109.9, 78.9, 78.6, 44.5, 35.8, 33.7, 31.5, 27.1, 25.6, 25.2.
nmax (KBr)/cmꢀ1 2989, 2937, 2901, 1670, 1629, 1452, 1423,
1380, 1331, 1266, 1207, 1162, 1075, 1045, 974, 918, 875, 793,
726, 703. m/z (ESI, þve) 269 ([M þ Na]þ, 100 %), 247
([M þ H]þ, 22). HRMS m/z 247.1327; C15H18O3 [M þ H]þ
requires 247.1334.
Compound 33
A magnetically stirred solution of the previously reported
and epimeric mixture of alcohols[5] derived from compound 7

Chemoenzymatic Syntheses of Some Analogues of Platencin
M
Concentration of fraction B (Rf 0.3(5) in 3 : 7 v/v ethyl
acetate/hexane) afforded compound 35 (162 mg, 65 %) as a
white, crystalline solid, mp 133–1358C, [a]D þ13.9 (c 1.0,
CHCl3). dH (400 MHz, CDCl3) 7.29 (dd, J 10.0 and 1.5, 1H),
6.33 (t, J 8.0, 1H), 6.09 (d, J 10.0, 1H), 5.75 (d, J 8.0, 1H), 4.27
(m, 1H), 3.93 (dd, J 8.0 and 1.8, 1H), 2.90 (broad s, 1H), 2.36
(dd, J 16.2 and 4.3, 1H), 2.09 (ddd, J 16.2, 13.8, and 1.5, 1H),
1.93 (m, 1H), 1.73 (m, 1H), 1.36 (d, J 1.5, 3H), 1.29 (d, J 1.5,
3H), 0.95–0.88 (complex m, 1H). dC (101 MHz, CDCl3) 199.5,
152.0, 133.1, 129.7, 128.6, 109.1, 80.8, 78.6, 44.3, 43.4, 34.9,
33.7, 28.7, 25.6, 25.1. nmax (KBr)/cmꢀ1 2979, 2937, 2892, 1681,
1456, 1415, 1381, 1373, 1265, 1207, 1165, 1094, 1066, 996,
884, 828, 778, 726, 703, 647, 542, 514. m/z (ESI, þve) 301
(100 %), 269 ([M þ Na]þ, 50), 247 ([M þ H]þ, 51). HRMS m/z
247.1330; C15H18O3 [M þ H]þ requires 247.1334.
1.95–1.83 (complex m, 2H), 1.51 (s, 3H), 1.32 (s, 3H), 1.24 (s,
3H), 1.20 (s, 3H), 1.05 (complex m, 2H). dC (101 MHz, CDCl3)
213.9, 149.7, 125.8, 112.1, 78.2, 75.5, 48.5, 40.7, 35.4, 35.2,
26.8, 26.6, 26.2, 25.5, 24.9, 24.7, 19.2. nmax (KBr)/cmꢀ1 2978,
2937, 2902, 2871, 1713, 1462, 1379, 1263, 1207, 1162, 1064,
1088, 973, 877, 836. m/z (ESI, þve) 413 (100 %), 331 (75), 299
(52), 277 (39). HRMS m/z 299.1622. C17H24O3 [M þ Na]þ
requires 299.1623.
Compound 40
A magnetically stirred solution of enone 38 (195 mg,
0.75 mmol) in diethyl ether/t-butanol (5.0 mL of a 1 : 1 v/v
mixture) maintained at 08C under a nitrogen atmosphere was
treated, dropwise, with t-BuOK (1.5 mL of a 1.0 M solution in
t-butanol, 1.5 mmol). The resulting mixture was stirred at 08C
for 0.33 h before being treated, dropwise, with a solution of
t-butyl acrylate (223 mL, 1.49 mmol) in dry diethyl ether
(4.5 mL). The ensuing mixture was allowed to stir for another
0.4 h at 08C before being quenched with NH4Cl (15 mL of a
saturated aqueous solution) and then extracted with ethyl acetate
(3 ꢁ 10 mL). The combined organic phases were washed with
brine (1 ꢁ 7 mL), dried (MgSO4), filtered, and concentrated
under reduced pressure. The light-yellow oil thus obtained was
subjected to flash column chromatography (silica, 1 : 9 v/v ethyl
acetate/hexane elution) to afford, after concentration of the
relevant fractions (Rf 0.5 in 3 : 7 v/v ethyl acetate/hexane), a
Compounds 37, 38, and 39
A magnetically stirred solution of enone 36 (125 mg,
0.5 mmol) in THF/HMPA (7.5 mL of a 4 : 1 v/v mixture)
maintained under an argon atmosphere was cooled to ꢀ788C
and then treated, dropwise, with KHMDS (1.25 mL of a 0.5 M
solution in toluene, 0.63 mmol). The ensuing mixture was
allowed to stir at ꢀ788C for 0.3 h before being treated, dropwise,
with iodomethane (225 mL, 3.5 mmol) then stirred at ꢀ788C for
0.3 h. The ensuing mixture was allowed to warm to 08C over a
period of 0.5 h before being quenched with NaHCO3 (10 mL of
saturated aqueous solution) and extracted with ethyl acetate
(3 ꢁ 15 mL). The combined organic phases were dried
(MgSO4), filtered, and concentrated under reduced pressure
and the clear, light-yellow oil thus obtained subjected to semi-
preparative HPLC (see General Experimental Procedures above
for details) to afford three fractions, A–C.
Concentration of fraction A (Rt 6.3 min) afforded compound
38 (66 mg, 51 %) as a white, crystalline solid, mp 118–1218C,
[a]D þ66.9 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 5.93 (t, J 2.0,
1H), 4.23 (dd, J 8.1 and 1.5, 1H), 4.13 (m, 1H), 2.60–2.46
(complex m, 2H), 2.35 (m, 1H), 2.15 (dd, J 14.0 and 5.4, 1H),
2.11–1.99 (complex m, 2H), 1.91 (m, 1H), 1.55 (s, 3H), 1.44 (s,
3H), 1.40–1.23 (complex m, 3H), 1.11 (d, J 6.6, 3H). dC
(101 MHz, CDCl3) 200.5, 164.7, 126.3, 109.6, 75.5, 73.9,
38.3, 37.6, 36.7, 31.4, 30.4, 26.0, 25.3, 24.5, 18.9, 14.8. nmax
(KBr)/cmꢀ1 2963, 2937, 2920, 2872, 1668, 1631, 1460, 1374,
1261, 1209, 1164, 1078, 1059, 1028, 921, 879, 848, 830, 518.
m/z (EI, 70 eV) 263 (25 %), 262 (Mþꢃ, 75), 249 (43), 248 (92),
247 (51), 233 (100). HRMS m/z 262.1566; C16H22O3 Mþꢃ
requires 262.1569.
Concentration of fraction B (Rt 6.7 min) afforded compound
37 (30 mg, 23 %) as a white, crystalline solid, mp 153–1598C,
[a]D þ31.5 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 5.96 (t, J 2.0,
1H), 4.28 (dd, J 8.2 and 4.2, 1H), 3.80 (dd, J 8.2 and 1.9, 1H), 2.52
(m, 1H), 2.41 (m, 1H), 2.34–2.18 (complex m, 2H), 2.01–1.87
(complex m, 3H), 1.62–1.59 (complex m, 3H), 1.57 (s, 3H), 1.38
(s, 3H), 1.10 (d, J 6.7, 3H). dC (101 MHz, CDCl3) 200.8, 163.8,
126.0, 109.4, 79.3, 75.8, 39.3, 39.0, 36.6, 32.6, 30.1, 25.9, 24.4,
21.8, 18.8, 14.8. nmax (KBr)/cmꢀ1 2963, 2932, 2907, 2872, 1673,
1634, 1459, 1375, 1263, 1205, 1152, 1068, 1047, 978, 945, 877,
848. m/z (ESI, þve) 547 (47 %), 317 (50), 285 (100), 263 (70).
HRMS m/z 262.1568; C16H22O3 Mþꢃ requires 262.1569.
Concentration of fraction C (Rt 7.1 min) gave compound 39
(9 mg, 7 %) as a white, crystalline solid, mp 160–1628C, [a]D
þ15.4 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 6.05 (d, J 6.9,
1H), 4.04 (m, 1H), 3.87 (dd, J 8.4 and 1.7, 1H), 2.77 (m, 1H),
2.50–2.39 (complex m, 2H), 2.17–2.01 (complex m, 2H),
1
clear, colourless oil. H NMR spectroscopic analysis of this
material suggested it comprised a . 6 : 1 mixture of esters 40
and 41. Subjection of this material to semi-preparative HPLC
(see General Experimental Procedures above for details) and
concentration of the appropriate fractions (Rt 10.7 min) afforded
compound 40 (167 mg, 57 %) as a white foam, [a]D þ10.3 (c 1.0,
CHCl3). dH (400 MHz, CDCl3) 4.14 (dd, J 8.2 and 3.7, 1H), 3.97
(d, J 8.2, 1H), 2.64–1.60 (complex m, 12H), 1.53 (s, 1H), 1.42
(s, 9H), 1.42–1.24 (complex m, 9H) (one resonance obscured or
overlapping). dC (101 MHz, CDCl3) 201.9, 173.0, 156.5, 132.6,
109.2, 80.3, 78.4, 75.5, 42.6, 39.9, 37.4, 34.2, 33.8, 31.1, 30.5,
30.0, 28.3, 26.1, 25.9, 25.1, 24.3. nmax (KBr)/cmꢀ1 2977, 2934,
1728, 1674, 1458, 1368, 1296, 1260, 1207, 1153, 1119, 1066,
975, 876, 848, 756. m/z (EI, 70 eV) 390 (Mþꢃ, 5 %), 375 (25),
334 (90), 317 (56), 203 (95), 159 (80), 57 (100). HRMS m/z
391.2489; C23H34O5 [M þ H]þ requires 391.2484.
Compound 43
A magnetically stirred solution of acetonide 42 (285 mg,
0.72 mmol) in THF/methanol/water (9 mL of 3:1:3 v/v/v
mixture) was treated with DOWEX-50 resin (350 mg of material
that had been rinsed successively with 1 M aqueous hydrochlo-
ric acid, water, saturated sodium bicarbonate solution, and
water). The resulting suspension was heated at 658C for 36 h
and then cooled, filtered, and the solids thus retained rinsed with
dichloromethane (3 ꢁ 25 mL) and then methanol (3 ꢁ 15 mL).
The combined filtrates were dried (MgSO4), filtered, and
concentrated under reduced pressure and the resulting clear,
colourless oil was subjected to flash column chromatography
(silica, 1 : 9 - 3 : 7 v/v ethyl acetate/hexane gradient elution) to
afford two fractions, A and B.
Concentration of fraction A (Rf 0.6 in 3 : 7 v/v ethyl acetate/
hexane) afforded the starting acetonide 42 (59 mg, 21 % recov-
ery) as a clear, colourless oil that was identical, in all respects,
with authentic material.
Concentration of fraction B (Rf 0.4 in 1 : 1 : 0.1 v/v ethyl
acetate/hexane/acetic acid) afforded diol 43 (154 mg, 61 %

N
R. N. Muhammad et al.
at 79 % conversion) as a thick, white foam, [a]D þ3.5 (c
1.0, CHCl3). dH (400 MHz, CDCl3) 6.82 (d, J 10.2, 1H),
5.88 (d, J 10.2, 1H), 3.95 (m, 1H), 3.40 (m, 1H), 3.22 (br s,
1H), 2.63 (br s, 1H), 2.17 (m, 1H), 2.06–1.85 (complex m,
6H), 1.79–1.59 (complex m, 5H), 1.41 (s, 9H), 1.01 (s, 3H).
dC (101 MHz, CDCl3) 203.7, 173.2, 152.6, 126.4, 80.6,
72.6, 67.5, 47.3, 42.1, 39.0, 32.8, 30.6, 28.2, 27.2, 25.1,
19.8, 18.2(3), 18.1(9). nmax (KBr)/cmꢀ1 3280, 2929, 2912,
1725, 1671, 1450, 1376, 1366, 1293, 1155, 1143, 1109,
1072, 1054, 1018, 967, 873, 844, 829, 700. m/z (ESI, þve)
723 (35 %), 373 ([M þ Na]þ, 75), 351 ([M þ H]þ, 52), 295
(60), 242 (100). HRMS m/z 373. 1991; C20H30O5 [M þ H]þ
requires 373. 1991.
Compound 46
A solution of freshly prepared VCl3ꢂ(THF)3 (188 mg,
0.50 mmol) in dry toluene (2.5 mL) maintained at 228C was
treated with activated[24] zinc dust (33 mg, 0.50 mmol) and the
resulting mixture irradiated in an ultrasonic bath (Branson
Model B2500R-DTH). After 0.33 h a solution of acetate 45
(97 mg, 0.25 mmol) in toluene (1.5 mL) was added to the
reaction mixture and sonication continued for 0.66 h. The
reaction mixture was then cooled to 228C before being diluted
with ethyl acetate (5.0 mL) and the resulting mixture passed
through a short plug of TLC grade silica that was then washed
with ethyl acetate (3 ꢁ 5 mL). The combined filtrates were
washed with water (1 ꢁ 10 mL), dried (MgSO4), filtered, and
concentrated under reduced pressure. The yellow oil thus
obtained was subjected to flash column chromatography (silica,
1 : 4 v/v ethyl acetate/hexane elution) to afford, after concentra-
tion of the relevant fractions (Rf 0.4), compound 46[19] (70 mg,
83 %) as a thick, white foam, [a]D þ19.1 (c 0.5, CHCl3). dH
(400 MHz, CDCl3) 6.48 (d, J 10.1, 1H), 5.90 (d, J 10.1, 1H), 2.52
(br s, 1H), 2.31 (d, J 18.1, 1H), 2.22 (m, 2H), 2.10–1.92
(complex m, 9H), 1.67 (m, 1H), 1.43 (s, 9H), 1.03 (s, 3H). dC
(101 MHz, CDCl3) 213.6, 202.8, 172.8, 151.1, 126.5, 80.5, 52.6,
47.2, 46.0, 43.2, 38.1, 30.1, 28.1, 26.1, 26.0, 25.6, 23.0, 18.0.
nmax (KBr)/cmꢀ1 2975, 2937, 2875, 2850, 1724, 1673, 1455,
1367, 1257, 1147, 917, 849, 830, 732, 648, 532. m/z (ESI, þve)
355 ([M þ Na]þ, 100 %). HRMS m/z 355.1883; C20H28O4
[M þ Na]þ requires 355.1885.
Compound 44
A magnetically stirred solution of diol 43 (127 mg,
0.55 mmol) in dichloromethane (9 mL) was cooled to 08C then
treated with p-TsOHꢂH2O (260 mg, 1.37 mmol). 4-Acetamido-
TEMPO (315 mg, 1.37 mmol) was then added, in portions over
0.5 h, to the reaction mixture that was stirred at 08C for 1 h and
then at 228C for 1 h before being quenched with NaHCO3
(10 mL of a saturated aqueous solution) and extracted with
dichloromethane (5 ꢁ 10 mL). The combined organic extracts
were dried (MgSO4), filtered, and concentrated under reduced
pressure to give a clear, light-orange oil. Subjection of this
material to flash column chromatography (silica, 1 : 4 v/v ethyl
acetate/hexane elution) and concentration of the appropriate
fractions (Rf 0.6 in 3 : 7 v/v ethyl acetate/hexane) afforded
acyloin 44 (163 mg, 85 %) as thick, yellow foam, [a]D þ95.3 (c
1.0, CHCl3). dH (400 MHz, CDCl3) 6.87 (d, J 10.3, 1H), 5.95
(d, J 10.3, 1H), 3.31 (s, 1H), 3.28 (s, 1H), 2.60 (br s, 1H), 2.23
(m, 1H), 2.12–1.81 (complex m, 10H), 1.41 (s, 9H), 1.04 (s,
3H). dC (101 MHz, CDCl3) 216.5, 202.6, 173.0, 149.3, 127.1,
80.7, 79.0, 47.4, 44.1, 42.4, 41.9, 30.3, 28.2, 26.4, 25.6, 24.3,
20.5, 18.3. nmax (KBr)/cmꢀ1 3437, 2987, 2949, 2873, 1728,
1670, 1439, 1386, 1360, 1294, 1233, 1197, 1173, 1062, 1035,
993, 954, 851, 827, 732, 706. m/z (ESI, þve) 371 ([M þ Na]þ,
100 %). HRMS m/z 371.1835; C20H28O5 [M þ H]þ requires
371.1834.
Compounds 49 and 50
A magnetically stirred solution of enone 48 (551 mg,
2.10 mmol) in distilled diethyl ether and t-butanol (21 mL of
2 : 1 v/v mixture) maintained at ꢀ108C under an argon
atmosphere was treated, dropwise, with t-BuOK (5.25 mL
of a 1.0 M solution in t-butanol, 5.25 mmol). The ensuing
mixture was stirred at ꢀ108C for 0.2 h before being treated,
via syringe pump, with a solution of methyl acrylate
(1.42 mL, 15.75 mmol) in diethyl ether (15 mL). The mixture
thus obtained was allowed to stir for 0.3 h and then treated
with NH4Cl (15 mL of a saturated aqueous solution) before
being extracted with diethyl ether (5 ꢁ 15 mL). The combined
organic fractions were washed with brine (1 ꢁ 15 mL) then
dried (Na2SO4), filtered, and concentrated under reduced
pressure. The resulting light-yellow oil was subjected to flash
column chromatography (silica, 1 : 9 v/v ethyl acetate/hexane
elution) to afford, after concentration of the relevant fractions
(Rf 0.4 in 3 : 7 v/v ethyl acetate/hexane), a clear colourless
oil. Subjection of this material to semi-preparative HPLC (see
General Experimental Procedures above for details) afforded
two fractions, A and B.
Concentration of fraction A (Rt 7.5 min) afforded compound
49 (526 mg, 72 %) as a clear, colourless oil, [a]D þ19.5 (c 1.0,
CHCl3). dH (400 MHz, CDCl3) 6.73 (d, J 10.2, 1H), 5.88 (d, J
10.2, 1H), 4.18 (m, 1H), 3.68 (dd, J 8.1 and 1.6, 1H), 3.65 (s, 3H),
2.29–2.12 (complex m, 3H), 2.05–1.81 (complex m, 3H), 1.74
(td, J 9.6 and 1.4, 1H), 1.68–1.60 (complex m, 3H), 1.54 (s, 3H),
1.35 (s, 3H), 1.33–1.23 (complex m, 2H), 1.19 (s, 3H). dC
(101 MHz, CDCl3) 203.3, 174.0, 152.3, 127.0, 109.4, 79.4,
75.5, 51.8, 47.3, 37.6, 36.6, 30.5, 29.5(9), 29.5(6), 25.9, 24.4,
23.7, 21.3, 19.4, 18.5. nmax (KBr)/cmꢀ1 3025, 2976, 2933, 2873,
1738, 1673, 1469, 1454, 1438, 1381, 1306, 1260, 1207, 1166,
1131, 1116, 1086, 1067, 1033, 992, 931, 875, 826, 811, 709. m/z
(EI, 70 eV) 348 (Mþꢃ, 20 %), 333(32), 261 (42), 203 (100),
Compound 45
A magnetically stirred solution of acyloin 44 (159 mg,
0.45 mmol) in anhydrous dichloromethane (3.5 mL) was treated
with DMAP (25 mg, 0.2 mmol) and then acetic anhydride
(51 mL, 0.54 mmol) and the ensuing mixture stirred at 228C
for 3.5 h. The reaction mixture was then diluted with dichlor-
omethane (10 mL) before being washed with brine (1 ꢁ 7 mL),
dried (MgSO4), filtered, and concentrated under reduced pres-
sure. The resulting light-yellow oil was subjected to flash
column chromatography (silica, 1 : 9 v/v ethyl acetate/hexane)
to afford, after concentration of the appropriate fractions (Rf 0.5
in 2 : 3 v/v ethyl acetate/hexane), compound 45 (133 mg, 75 %)
as a clear, colourless foam, [a]D þ105.0 (c 1.0, CHCl3). dH
(400 MHz, CDCl3) 6.87 (d, J 10.3, 1H), 5.95 (d, J 10.3, 1H), 4.74
(s, 1H), 2.57 (br s, 1H), 2.23 (m, 1H), 2.19 (s, 3H), 2.12–1.81
(complex m, 7H), 1.41 (s, 9H), 1.04 (s, 3H). dC (101 MHz,
CDCl3) 209.6, 201.8, 172.9, 169.9, 146.9, 127.6, 80.7, 47.4,
43.7, 42.8, 41.0, 30.2, 29.8, 28.3, 26.4, 24.7, 24.4, 21.3, 20.8,
18.3. nmax (KBr)/cmꢀ1 2929, 1754, 1729, 1675, 1369, 1219,
1152, 1112, 1050, 977, 849. m/z (ESI, þve) 445 (100 %), 413
([M þ Na]þ, 50). HRMS m/z 413.1940; C22H30O6 [M þ H]þ
requires 413.1940.

Chemoenzymatic Syntheses of Some Analogues of Platencin
O
175 (68), 159 (85). HRMS m/z 348.1937; C20H28O5 Mþꢃ
requires 348.1937.
coloured foam, [a]D þ15.9 (c 1.0, CHCl3). dH (400 MHz,
CDCl3) 6.92 (d, J 10.3, 1H), 5.98 (d, J 10.3, 1H), 3.64 (s,
3H), 3.38 (s, 1H), 3.17 (s, 1H), 2.57 (m, 1H), 2.24–2.14
(complex m, 2H), 2.10–1.59 (complex m, 8H), 1.42 (m, 1H),
1.25 (s, 3H). dC (101 MHz, CDCl3) 216.2, 202.6, 173.8, 149.6,
127.7, 78.8, 51.8, 47.5, 41.9(3), 41.9(0), 38.2, 30.3, 29.4, 25.8,
23.7, 21.1, 20.4. nmax (KBr)/cmꢀ1 3450, 2950, 2875, 1731,
1671, 1469, 1439, 1387, 1364, 1295, 1232, 1198, 1175, 1103,
1061, 993, 929, 851, 828, 752, 707, 577. m/z (ESI, þve) 361
(100 %), 329 ([M þ Na]þ, 61), 307 (60), 275 (70). HRMS m/z
329.1363; C17H22O5 [M þ Na]þ requires 329.1365.
Concentration of fraction B (Rt 9.7 min) afforded compound
50 (100 mg, 14 %) as a clear, colourless and viscous oil, [a]D
þ11.7 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 6.72 (d, J 10.2, 1H),
5.87 (d, J 10.2, 1H), 4.19 (m, 1H), 3.66 (m, 1H), 3.64 (s, 3H),
2.30 (m, 1H), 2.14 (m, 1H), 2.06–1.75 (complex m, 6H), 1.65 (m,
4H), 1.55 (s, 3H), 1.25 (s, 3H), 1.05 (s, 3H). dC (101 MHz,
CDCl3) 203.2, 174.2, 152.1, 126.4, 109.4, 79.7, 75.6, 51.8, 47.3,
42.8, 37.7, 29.9, 29.3, 26.9, 25.9, 24.4, 24.1, 19.8, 18.6, 18.5. nmax
(KBr)/cmꢀ1 2925, 2873, 1738, 1673, 1461, 1375, 1294, 1260,
1206, 1170, 1118, 1067, 974, 931, 877, 824, 806, 704.
Compound 53
Compound 51
A magnetically stirred solution of acyloin 52 (125 mg,
0.41 mmol), triethylamine (1.7 mL), and DMAP (124 mg,
1.02 mmol) in dichloromethane (7 mL) was cooled to 08C and
then treated with benzoyl chloride (119 mL, 1.02 mmol). The
resulting mixture was allowed to warm to 228C, stirred vigor-
ously at this temperature for 16 h, and then treated with HCl
(15 mL of a 1 M aqueous solution) before being extracted with
dichloromethane (5 ꢁ 15 mL). The combined organic phases
were washed with brine (1 ꢁ 15 mL) then dried (Na2SO4),
filtered, and concentrated under reduced pressure. The result-
ing light-yellow oil was subjected to flash column chromatog-
raphy (silica, 1 : 9 v/v ethyl acetate/hexane elution) and
concentration of the appropriate fractions (Rf 0.6 in 3 : 7 v/v
ethyl acetate/hexane) gave compound 53 (147 mg, 89 %) as a
clear, colourless foam, [a]D þ91.5 (c 1.0, CHCl3). dH
(400 MHz, CDCl3) 8.11–8.02 (complex m, 2H), 7.62 (m,
1H), 7.51–7.45 (complex m, 2H), 6.51 (d, J 10.3, 1H), 5.96
(d, J 10.3, 1H), 5.04 (s, 1H), 3.66 (s, 3H), 2.67 (s, 1H), 2.33–
1.98 (complex m, 9H), 1.84 (m, 1H), 1.96 (m, 1H), 1.28 (s, 3H).
dC (101 MHz, CDCl3) 209.2, 202.0, 173.7, 165.6, 147.4, 133.9,
130.1, 129.0, 128.8, 128.1, 77.1, 51.9, 47.5, 42.5, 41.3, 37.7,
30.1, 29.3, 24.8, 23.9, 21.3, 21.2. nmax (KBr)/cmꢀ1 2948, 2874,
1729, 1674, 1601, 1468, 1451, 1390, 1314, 1253, 1197, 1176,
1108, 1069, 1026, 988, 803, 710. m/z (ESI, þve) 465 (63 %),
433 ([M þ Na]þ, 100), 411 (35). HRMS m/z 433.1629;
C24H26O6 [M þ H]þ requires 433.1627.
A magnetically stirred solution of acetonide 49 (501 mg,
1.44 mmol) in methanol/water (21 mL of a 4 : 1 v/v mixture) was
treated with DOWEX-50 resin (575 mg of acidified material).
The ensuing mixture was heated at 658C for 56 h then cooled to
228C, and the DOWEX-50 resin removed by filtration and
washed with methanol (3 ꢁ 15 mL). The combined filtrates
were concentrated under reduced pressure and the aqueous
residue diluted with brine (15 mL) and extracted with dichlor-
omethane (5 ꢁ 30 mL). The combined organic fractions were
then dried (MgSO4), filtered, and concentrated under reduced
pressure. Subjection of the ensuing light-yellow oil to flash
column chromatography (silica, 3 : 7 v/v ethyl acetate/hexane
elution) afforded two fractions, A and B.
Concentration of fraction A (Rf 0.4 in 3 : 7 v/v ethyl acetate/
hexane) afforded the starting ester 49 (75 mg, 15 % recovery) as
a clear, colourless oil that was identical, in all respects, to
authentic material.
Concentration of fraction B (Rf 0.4 in 4 : 1 v/v ethyl acetate/
hexane) afforded diol 51 (345 mg, 78 % at 85 % conversion) as a
thick, white foam, [a]D þ2.4 (c 1.0, CHCl3). dH (400 MHz,
CDCl3) 6.84 (d, J 10.2, 1H), 5.89 (d, J 10.2, 1H), 3.96 (m, 1H),
3.66 (s, 3H), 3.43 (m, 1H), 3.22 (d, J 4.3, 1H), 2.58 (br s, 1H),
2.31–2.08 (complex m, 3H), 1.94–1.85 (complex m, 3H), 1.78–
1.40 (complex m, 6H), 1.18 (s, 3H). dC (101 MHz, CDCl3)
203.5, 174.2, 152.8, 126.9, 72.4, 67.4, 51.8, 47.2, 38.8, 36.1,
32.6, 30.0, 29.5, 24.7, 21.7, 19.3, 18.2. nmax (KBr)/cmꢀ1 3297,
2924, 2869, 1737, 1668, 1450, 1435, 1417, 1376, 1294, 1263,
1192, 1092, 1069, 1055, 1013, 970, 944, 903, 868, 827, 795,
762,. m/z (ESI, þve) 639 (100 %), 331 ([M þ Na]þ, 80). HRMS
m/z 331.1516; C17H24O5 [M þ H]þ requires 331.1521.
Compound 54
A vigorously stirred solution of methyl triphenylphospho-
nium bromide (89 mg, 0.25 mmol) in freshly distilled THF
(5 mL) maintained at 08C was treated, dropwise via syringe, with
KHMDS (650 mL of a 0.5 M solution in toluene). The resulting
yellow solution was stirred for 0.5 h, warmed to 228C over 0.5 h,
and then cooled to ꢀ788C. A solution of keto-ester 53 (55 mg,
0.13 mmol) in THF (2.5 mL) was then added, dropwise, to the
reaction mixture after which it was stirred at ꢀ788C for a further
1.5 h before being quenched with NH4Cl (10 mL of saturated
aqueous solution). After warming the mixture was extracted
with diethyl ether (5 ꢁ 5 mL) and the combined organic phases
were washed with brine (1 ꢁ 5 mL), dried (Na2SO4) then
filtered, and concentrated under a stream of nitrogen. Subjection
of the ensuing light-yellow oil to flash column chromatography
(silica, 1 : 4 v/v ethyl acetate/hexane elution) afforded, after
concentration of the appropriate fractions (Rf 0.6), compound 54
(37.8 mg, 71 %) as a clear, colourless foam, [a]D þ21.3 (c 1.0,
CHCl3). dH (400 MHz, CDCl3) 8.07 (m, 2H), 7.60 (m, 1H), 7.48
(t, J 7.6, 2H), 6.55 (d, J 10.3, 1H), 5.90 (d, J 10.3, 1H), 5.38
(s, 1H), 5.21 (s, 1H), 5.12 (s, 1H), 3.66 (s, 3H), 2.59 (s, 1H),
2.32–2.05 (complex m, 4H), 2.01–1.25 (complex m, 7H), 1.23
Compound 52
A magnetically stirred mixture of p-TsOHꢂH2O (390 mg,
2.1 mmol) and 4-acetamido-TEMPO (466 mg, 1.5 mmol) in
dichloromethane (25 mL) was maintained at 228C for 0.5 h and
the resulting suspension added, in portions, to a magnetically
stirred solution of compound 51 (308 mg, 1.0 mmol) in
dichloromethane (25 mL) maintained at 08C. The resulting
mixture was stirred at 08C for a further 2 h before being treated
with NaHCO3 (25 mL of a saturated aqueous solution). The
separated aqueous phase was extracted with dichloromethane
(4 ꢁ 75 mL) and the combined organic fractions washed with
water (1 ꢁ 15 mL) and brine (1 ꢁ 15 mL) before being dried
(Na2SO4), filtered, and concentrated under reduced pressure.
The resulting clear, light-yellow oil was subjected to flash
column chromatography (silica, 3 : 7 v/v ethyl acetate/hexane
elution) to afford, after concentration of the appropriate frac-
tions (Rf 0.4), acyloin 52 (285 mg, 93 %) as a thick, light-yellow

P
R. N. Muhammad et al.
(s, 3H). dC (101 MHz, CDCl3) 203.0, 174.1, 166.5, 149.8, 148.5,
133.4, 130.3, 129.9, 128.7, 127.6, 114.6, 76.0, 51.8, 47.3, 39.1,
37.1, 35.5, 30.0, 29.4, 27.5, 25.9, 22.0, 21.0. nmax (KBr)/cmꢀ1
2956, 2929, 2854, 1740, 1720, 1677, 1464, 1452, 1442, 1377,
1261, 1179, 1110, 1072, 1027, 975, 804, 711. m/z (ESI, þve) 431
([M þ Na]þ, 100 %), 409 (42). HRMS m/z 431.1844; C25H28O5
[M þ H]þ requires 431.1834.
treated with dry triethylamine (120 mL, 0.88 mmol) and HATU
(263 mg, 0.69 mmol). After 16 h the reaction mixture was
quenched with brine (1.9 mL) and then extracted with chloro-
form (3 ꢁ 10 mL). The combined organic phases were dried
(Na2SO4), filtered, and concentrated under reduced pressure.
The ensuing dark residue was subjected to flash column
chromatography (silica, 1 : 10 v/v ethyl acetate/hexane elution)
and concentration of the relevant fractions (Rf 0.6 in 3 : 7 v/v
ethyl acetate/hexane) afforded amide 57 (39.2 mg, 32 %) as
light-yellow and viscous film, [a]D ꢀ5.9 (c 0.1, CHCl3). dH
(400 MHz, CDCl3) 11.84 (s, 1H), 11.01 (br s, 1H), 8.12 (s, 1H),
7.56 (d, J 9.0, 1H), 6.75 (d, J 10.2, 1H), 6.50 (d, J 9.0, 1H), 5.94
(d, J 10.2, 1H), 4.42 (m, 2H), 4.19 (m, 1H), 3.70 (dd, J 8.0 and
1.6, 1H), 2.41 (m, 2H), 2.22 (m, 1H), 2.09–1.27 (complex m,
9H), 1.55 (s, 3H), 1.35 (s, 3H), 1.24 (s, 3H), 1.16–1.09 (complex
m, 2H), 0.08 (s, 9H). dC (101 MHz, CDCl3) 203.9, 174.0, 170.6,
154.8, 154.1, 152.9, 127.6, 126.9, 114.5, 111.3, 109.5, 104.6,
79.4, 75.4, 63.9, 47.8, 37.7, 36.9, 32.7, 31.6, 29.6, 25.9, 24.4,
23.8, 21.1, 19.4, 18.5, 17.5, ꢀ1.3. nmax (KBr)/cmꢀ1 3319, 2924,
2807, 1654, 1597, 1535, 1467, 1385, 1331, 1292, 1259, 1208,
1147, 1115, 1087, 1064, 969, 932, 859, 837, 789. m/z (EI, 70 eV)
585 (Mþꢃ, 5 %), 570 (5), 317 (100), 259 (38), 241 (42), 204 (31),
151 (42), 73 (48). HRMS m/z 585.2755; C31H43NO8Si Mþꢃ
requires 585.2758.
Compound 55
A magnetically stirred solution of ester 49 (87 mg,
0.25 mmol) in THF (10 mL) maintained at 508C was treated
with LiOH (10 mL of a 1 M aqueous solution) and the ensuing
mixture stirred at this temperature for 5 h. The cooled reaction
mixture was treated with water (15 mL) and brine (10 mL)
before being washed with diethyl ether (1 ꢁ 20 mL). The
separated aqueous layer was then acidified with HCl (15 mL
of a 1 M aqueous solution) and extracted with diethyl ether
(10 ꢁ 5 mL). The combined organic extracts were dried
(Na2SO4), filtered, and then concentrated under reduced pres-
sure and the residue thus obtained subjected to flash column
chromatography (silica, 55 : 45 v/v ethyl acetate/hexane elu-
tion). Concentration of the appropriate fractions (Rf 0.2 in 1 : 1 v/
v ethyl acetate/hexane) gave acid 55 (81 mg, 97 %) as a clear,
colourless and viscous foam, [a]D þ6.1 (c 1.0, CHCl3). dH
(400 MHz, CDCl3) 6.74 (d, J 10.1, 1H), 5.89 (d, J 10.1, 1H), 4.19
(m, 1H), 3.69 (d, 1H), 2.34–2.12 (complex m, 3H), 2.03 (m, 1H),
1.96–1.81 (complex m, 2H), 1.77–1.55 (complex m, 5H), 1.52
(s, 3H), 1.35 (s, 3H), 1.33–1.23 (complex m, 2H), 1.19 (s, 3H).
dC (101 MHz, CDCl3) 203.5, 179.1, 152.5, 126.9, 109.4, 79.4,
75.4, 47.3, 37.6, 36.7, 30.2, 29.6, 29.5, 25.9, 24.4, 23.7, 21.2,
19.4, 18.5. nmax (KBr)/cmꢀ1 2978, 2934, 1708, 1673, 1469,
1454, 1440, 1381, 1311, 1280, 1260, 1208, 1164, 1131, 1116,
1087, 1066, 1033, 970, 931, 874, 826, 754. m/z (EI, 70 eV) 334
(Mþꢃ, ,1 %), 318 (90), 260 (40), 207 (100). HRMS m/z
334.1767; C19H26O5 Mþꢃ requires 334.1780.
Compound 58
A magnetically stirred solution of compound 57 (29 mg,
0.05 mmol) in DMF (500 mL) maintained under a nitrogen
atmosphere at 228C was treated with TASF (28 mg, 0.10 mmol).
The ensuing mixture was heated at 408C for 1 h then cooled, and
quenched with brine (4 mL). The separated aqueous phase was
extracted with chloroform (5 ꢁ 5 mL) and the combined organic
fractions were then dried (Na2SO4), filtered, and concentrated
under reduced pressure. The residue thus obtained was subjected
to flash column chromatography (silica, 8 : 12 : 0.1 : 0.1 : 0.1 v/v
ethyl acetate/hexane/acetic acid/methanol/water elution) and
concentration of the relevant fractions (Rf 0.3 in 80 : 20 :
0.5 : 1.0 : 0.5 v/v ethyl acetate/ hexane/acetic acid/methanol/
water) afforded compound 58 (5 mg, 21 %) as a light-brown
foam, [a]D ꢀ29.0 (c 0.1, CHCl3). dH (400 MHz, CDCl3) 11.86
(s, 1H), 11.12 (s, 1H), 8.20 (s, 1H), 7.63 (dd, J 8.9 and 0.8, 1H),
6.82 (d, J 10.1, 1H), 6.52 (dd, J 8.9 and 0.7, 1H), 5.96 (dd, J 10.1
and 0.7, 1H), 4.21 (m, 1H), 3.71 (m, 1H), 2.51–2.35 (complex m,
2H), 2.21 (m, 1H), 2.12–1.29 (complex m, 6H), 1.55 (s, 3H),
1.36 (s, 3H), 1.27 (m, 3H), 1.26 (s, 3H) (resonance due to amide
or OH group proton not observed). dC (101 MHz, CDCl3) 205.2,
174.0, 172.8, 155.5, 154.6, 154.3, 128.5, 126.7, 114.5, 111.4,
109.5, 103.6, 79.3, 75.4, 47.8, 37.8, 36.7, 32.5, 31.8, 29.5, 25.9,
24.4, 23.7, 21.4, 19.5, 18.5. nmax (KBr)/cmꢀ1 2928, 2859, 1654,
1537, 1451, 1379, 1259, 1064, 875, 795. m/z (ESI, ꢀve) 484
([M – Hþ]ꢀ, 53 %), 96 (100). HRMS m/z 484.1971; C26H31NO8
[M – Hþ]ꢀ requires 484.1971.
Compound 56
A magnetically stirred solution of 2-(trimethylsilyl)ethyl
2,4-dihydroxy-3-nitrobenzoate[19] (1.00 g, 3.34 mmol) in ethyl
acetate/methanol (65 mL of a 5 : 1 v/v mixture) was treated with
acetic acid (190 mL) and 10 % palladium on carbon (185 mg).
The resulting suspension was stirred at 228C under a hydrogen
atmosphere for 16 h after which time it was filtered through a
pad of Celite that was washed with ethyl acetate (50 mL). The
combined filtrates were concentrated under reduced pressure to
afford a dark solid, recrystallisation (hexane) of which afforded
aniline 56[19] (710 mg, 79 %) as a grey solid, mp 1078C. dH
(400 MHz, CDCl3) 11.19 (s, 1H), 7.33 (d, J 8.3, 1H), 6.35 (d, J
8.3, 1H), 4.51–4.37 (complex m, 3H), 1.12 (m, 2H), 0.11 (s, 9H)
(resonances due to OH group protons not observed). dC
(101 MHz, CDCl3) 170.8, 153.0, 151.3, 122.0, 121.1, 106.9,
106.2, 63.6, 17.5, ꢀ1.30. nmax (KBr)/cmꢀ1 3381, 3310, 3110,
2954, 2900, 1661, 1625, 1506, 1468, 1387, 1288, 1250, 1217,
1175, 1143, 1062, 1044, 941, 860, 837, 778, 694. m/z (EI, 70 eV)
269 (Mþꢃ, 5 %), 267 (8), 241 (21), 226 (19), 152 (31), 151 (100),
73 (41). HRMS m/z 269.1084; C12H19NO4 Mþꢃ requires
269.1083.
Compound 59
A magnetically stirred solution of ester 50 (53 mg,
0.15 mmol) in THF (5 mL) maintained at 508C was treated with
LiOH (5 mL of a 1 M aqueous solution) and the ensuing mixture
stirred at this temperature for 5 h. After this time the reaction
mixture was cooled and treated with water (7 mL) and brine
(5 mL) before being washed with dichloromethane (2 ꢁ 10 mL).
The separated aqueous layer was acidified to pH 2 (with 1 M
aqueous HCl) and extracted with dichloromethane (7 ꢁ 4 mL).
Compound 57
A magnetically stirred solution of compound 55 (70 mg,
0.21 mmol) and aniline 56 (117 mg, 0.69 mmol) in DMF
(750 mL) maintained at 228C under an argon atmosphere was

Chemoenzymatic Syntheses of Some Analogues of Platencin
Q
The combined organic extracts were then dried (MgSO4),
filtered, and concentrated under reduced pressure. The residue
thus obtained was subjected to flash column chromatography
(silica, 55 : 45 v/v ethyl acetate/hexane elution) and concentra-
tion of the appropriate fractions (Rf 0.2 in 1 : 1 v/v ethyl acetate/
hexane) gave acid 59 (48 mg, 95 %) as a clear, colourless foam,
[a]D þ61.3 (c 1.0, CHCl3). dH (400 MHz, CDCl3) 6.72 (d, J 10.2,
1H), 5.88 (d, J 10.2, 1H), 4.19 (m, 1H), 3.65 (dd, J 8.1 and 1.6,
1H), 2.35 (m, 1H), 2.18 (m, 1H), 2.07–1.35 (complex m, 11H),
1.43 (s, 3H), 1.34 (s, 3H), 1.25 (s, 3H). dC (101 MHz, CDCl3)
203.2, 178.5, 152.3, 126.3, 109.5, 79.7, 75.6, 47.2, 42.7, 37.7,
30.5, 29.2, 26.7, 25.9, 24.4, 24.1, 19.9, 18.6, 18.5. nmax (KBr)/
cmꢀ1 2977, 2934, 2872, 1728, 1674, 1458, 1368, 1296, 1260,
material was identical, in all respects, with that obtained by
Method i described immediately above.
Compound 63
A magnetically stirred solution of compound 62[8] (63 mg,
0.19 mmol) and aniline 56 (101 mg, 0.60 mmol) in DMF
(0.67 mL) maintained at 228C under a nitrogen atmosphere
was treated with triethylamine (110 mL, 0.81 mmol) and HATU
(228 mg, 0.60 mmol). After 16 h the reaction mixture was
quenched with brine (1 mL) and extracted with chloroform
(3 ꢁ 5 mL). The combined organic phases were dried (Na2SO4),
filtered, and concentrated under reduced pressure. The dark-
coloured residue thus obtained was subjected to flash column
chromatography (silica, 1 : 10 v/v ethyl acetate/hexane elution)
and concentration of the relevant fractions (Rf ¼ 0.6 in 3 : 7 v/v
ethyl acetate/hexane) afforded amide 63 (16 mg, 14 %) as a
white film. This material was immediately subjected to treat-
ment with TASF as described below.
1153, 1119, 1066, 975, 876, 848, 755. m/z (EI, 70 eV) 334 (Mþꢃ
,
11 %), 319 (30), 233 (75), 190 (70), 146 (100), 121 (80). HRMS
m/z 334.1799; C19H26O5 Mþꢃ requires 334.1780.
Compound 61
Method i. A magnetically stirred solution of compound
59 (50 mg, 0.15 mmol) in acetonitrile (1.5 mL) maintained at
228C was treated with dry triethylamine (62 mL, 0.45 mmol),
DMAP (37 mg, 0.30 mmol), and DCC (230 mL of a 1.0 M
solution in freshly distilled dichloromethane, 0.23 mmol).
After 5 h a solution of 3-amino-2,4-dihydroxybenzoic
acid (60) (49.5 mg, 0.30 mmol) in DMF (350 mL) was
added to the reaction mixture and stirring continued for
another 36 h. The resulting mixture was concentrated under
reduced pressure and the residue thus obtained subjected to
flash column chromatography (silica, 80 : 20 : 1 : 0.5 : 0.5 v/v
ethyl acetate/hexane/methanol/acetic acid/water elution)
to afford, after concentration of the relevant fractions (Rf ¼ 0.3
in 80 : 20 : 0.5 : 1.0 : 0.5 v/v ethyl acetate/hexane/methanol/
acetic acid/water), compound 61 (15 mg, 21 %) as a light-
orange foam, [a]D ꢀ9.2 (c 0.1, CHCl3). dH (400 MHz, CDCl3)
11.90 (s, 1H), 11.31 (s, 1H), 8.09 (s, 1H), 7.63 (d, J 8.9, 1H),
6.85 (d, J 10.1, 1H), 6.51 (d, J 8.9, 1H), 5.97 (d, J 10.1, 1H),
4.22 (m, 1H), 3.68 (d, J 7.9, 1H), 2.52–1.26 (complex m, 12H),
1.36 (s, 6H), 1.15 (s, 3H) (resonance due to amide or OH group
proton not observed). dC (101 MHz, CDCl3) 205.5, 173.4,
172.4, 155.0, 154.6, 154.2, 128.2, 125.7, 114.2, 111.1, 109.4,
103.4, 79.3, 75.4, 47.5, 42.5, 37.9, 31.8, 29.7, 27.6, 25.8, 24.3,
23.9, 19.7, 18.5, 18.2. nmax (KBr)/cmꢀ1 3307, 2924, 2853,
1658, 1647, 1535, 1456, 1379, 1260, 1208, 1154, 1119, 1065,
910, 874, 799, 733, 608. m/z (ESI, ꢀve) 484 ([M – Hþ]ꢀ,
18 %), 134 (100), 105 (38). HRMS m/z 484.1970; C26H31NO8
[M – Hþ]ꢀ requires 484.1971.
Method ii. A magnetically stirred solution of compound 59
(21 mg, 0.063 mmol) in DMF (1.0 mL) maintained at 228C was
treated with DMAP (5 mg, 0.164 mmol) and EDC (15.4 mg,
0.081 mmol). After 5 h a solution of 3-amino-2,4-dihydroxy-
benzoic acid (60) (21.9 mg, 0.13 mmol) in DMF (250 mL) was
added to the reaction mixture and stirring continued for 36 h at
which point water (7 mL) was added and the pH of the ensuing
mixture was adjusted to 4 using HCl (1 M aqueous solution) and
then extracted with dichloromethane (5 ꢁ 10 mL). The combined
organic phases were dried (MgSO4), filtered, and concentrated
under reduced pressure. The ensuing light-yellow oil was sub-
jected to flash column chromatography (silica, 75 : 25 : 1 : 0.5 : 0.5
v/v ethyl acetate/hexane/methanol/acetic acid/water elution) to
afford, after concentration of the relevant fractions (Rf 0.3 in
80 : 20 : 0.5 : 1.0 : 0.5 v/v ethyl acetate/hexane/methanol/acetic
acid/water), compound 61 (8.2 mg, 27 %) as a thick foam. This
Compound 64
A magnetically stirred solution of TMSE amide 63 (12 mg,
0.02 mmol) in DMF (0.18 mL) maintained under a nitrogen
atmosphere at 228C was treated with TASF (11.2 mg,
0.04 mmol). The ensuing mixture was heated at 408C for 1 h
and then cooled and quenched with brine (2 mL). The separated
aqueous phase was extracted with chloroform (5 ꢁ 2 mL) and
the combined organic fractions were then dried (Na2SO4),
filtered, and concentrated under reduced pressure. The residue
thus obtained was subjected to flash column chromatography
(silica, 8 : 12 : 0.1 : 0.1 : 0.1 v/v ethyl acetate/hexane/acetic acid/
methanol/water elution) and concentration of the relevant frac-
tions (Rf 0.3 in 80 : 20 : 0.5 : 1.0 : 0.5 v/v ethyl acetate/hexane/
acetic acid/methanol/water) afforded compound 64 (1.5 mg,
15 %) as a white film, [a]D ꢀ24.0 (c 0.1, CHCl3). dH (400 MHz,
CDCl3) 11.52 (s, 1H), 11.24 (s, 1H), 8.32 (s, 1H), 7.63 (d, J 9.2,
1H), 6.54 (d, J 9.2, 1H), 4.20 (m, 1H), 3.64 (m, 1H), 2.68 (m,
1H), 2.48 (m, 2H), 2.27 (m, 1H), 2.04–1.73 (complex m, 6H),
1.63–1.51 (complex m, 3H), 1.52 (s, 3H), 1.36 (s, 3H), 1.31 (s,
3H) (resonances due to amide and OH group protons not
observed). dC (200 MHz, CDCl3) 217.4 (C), 174.3 (C), 172.9
(C), 155.7 (C), 154.5 (C), 128.3 (CH), 114.5 (C), 111.6 (CH),
108.8 (C), 103.1 (C), 82.2 (CH), 75.9 (CH), 51.0 (C), 41.0 (CH),
34.7 (C), 34.0 (CH2), 33.5 (CH2), 32.8 (CH2), 32.7 (CH2), 29.0
(CH), 25.8 (CH3), 24.2 (CH3), 20.4 (CH3), 19.7 (CH2), 19.1
(CH2) (one resonance obscured or overlapping). nmax (KBr)/
cmꢀ1 3292, 3072, 2933, 2619, 1696, 1654, 1597, 1534, 1453,
1380, 1260, 1241, 1209, 1153, 1062, 1038, 910, 875, 794, 732.
m/z (ESI, ꢀve) 486 ([M – Hþ]ꢀ, 100 %), 168 (10), 59 (24).
HRMS m/z 486.2129; C26H33NO8 [M – Hþ]ꢀ requires
486.2128.
X-Ray Crystallographic Studies
Crystallographic Data
Crystallographic Data for the Admixture of Compounds
15 and 32
C16H22O3, M 262.34, T 150 K, monoclinic, space group P21,
˚
Z 4, a 6.34903(17), b 9.1348(2), c 23.8101(7) A; b 95.882(3)8; V
3
1373.65(6) A , Dx 1.269 g cmꢀ3, 5468 unique data (2ymax
˚
148.28), R 0.039 [for 4880 reflections with I . 2.0s(I)]; Rw
0.095 (all data), S 1.01.

R
R. N. Muhammad et al.
Crystallographic Data for Compound 28
References
[1] For a very useful introduction to this topic, set in an historical context,
see: K. C. Nicolaou, S. Rigol, J. Antibiot 2018, 71, 153. doi:10.1038/
JA.2017.62
[2] For recent reviews see: (a) R. Shang, J. Liang, Y. Yi, J. Wang,
Molecules 2015, 20, 16127. doi:10.3390/MOLECULES200916127
(b) J. D. Rudolf, L.-B. Dong, B. Shen, Biochem. Pharmacol. 2017, 133,
139. doi:10.1016/J.BCP.2016.11.013
C17H24O3, M 276.38, T 150 K, orthorhombic, space group
˚
P212121, Z 4, a 6.4901(1), b 11.7812(1), c 18.7583(2) A; V
1434.28(3) A , Dx 1.280 g cmꢀ3, 2831 unique data (2ymax
3
˚
144.68), R 0.028 [for 2753 reflections with I . 2.0s(I)]; Rw
0.069 (all data), S 1.00.
[3] See, for example, (a) E. Martens, A. L. Demain, J. Antibiot 2011, 64,
Crystallographic Data for Compound 34
705. doi:10.1038/JA.2011.80
C15H18O3, M 246.31, T 150 K, monoclinic, space group P21,
˚
(b) L.-B. Dong, J. D. Rudolf, B. Shen, Org. Lett. 2016, 18, 4606 and
references cited therein. doi:10.1021/ACS.ORGLETT.6B02248
[4] K. Palanichamy, K. P. Kaliappan, Chem. Asian J. 2010, 5, 668. doi:10.
1002/ASIA.200900423
[5] K. A. B. Austin, M. G. Banwell, A. C. Willis, Org. Lett. 2008, 10, 4465.
doi:10.1021/OL801647H
[6] K. C. Nicolaou, G. S. Trai, D. J. Edmonds, Angew. Chem. Int. Ed. 2008,
Z 6, a 12.1619(3), b 8.3569(2), c 18.7928(4) A; b 97.273(2)8; V
3
1894.65(8) A , Dx 1.295 g cmꢀ3, 6248 unique data (2ymax
˚
144.88), R 0.033 [for 5917 reflections with I . 2.0s(I)]; Rw
0.081 (all data), S 1.00.
Crystallographic Data for Compound 35
47, 1780. doi:10.1002/ANIE.200800066
C15H18O3, M 246.31, T 150 K, monoclinic, space group P21,
˚
[7] For a summary of the ways in which such cis-1,2-dihydrocatechols
are produced and have been exploited in our group, see: E. S. Taher,
M. G. Banwell, J. N. Buckler, Q. Yan, P. Lan, Chem. Rec. 2018, 18,
239. doi:10.1002/TCR.201700064
[8] E.-L. Chang, B. D. Schwartz, A. G. Draffan, M. G. Banwell, A. C. Willis,
Chem. Asian J. 2015, 10, 427. doi:10.1002/ASIA.201403069
[9] R. N. Muhammad, A. G. Draffan, M. G. Banwell, A. C. Willis, Synlett
2016, 27, 61.
Z 4, a 6.2911(4), b 35.4329(15), c 6.4453(4) A; b 118.271(8)8; V
3
1265.36(16) A , Dx 1.293 g cmꢀ3, 2533 unique data (2ymax
˚
144.68), R 0.064 [for 2454 reflections with I . 2.0s(I)]; Rw
0.166 (all data), S 1.01.
Crystallographic Data for Compound 37
[10] Both the R- and the S-enantiomeric forms of compound 17
have been reported: (a) G. Sabitha, G. Chandrashekhar, J. S. Yadav,
K. Rachineni, B. Jagadeesh, RSC Adv. 2012, 2, 10157.
(b) T. Mahapatra, T. Das, S. Nanda, Bull. Chem. Soc. Jpn. 2011, 84,
511. doi:10.1039/C2RA21346J
[11] E. J. Corey, M. Chaykovsky, J. Am. Chem. Soc. 1965, 87, 1353.
doi:10.1021/JA01084A034
[12] J.-L. Luche, J. Am. Chem. Soc. 1978, 100, 2226. doi:10.1021/
JA00475A040
[13] J. Furukawa, N. Kawabata, J. Nishimura, Tetrahedron 1968, 24, 53.
doi:10.1016/0040-4020(68)89007-6
[14] R. E. Ireland, L. Liu, J. Org. Chem. 1993, 58, 2899. doi:10.1021/
JO00062A040
[15] For recent applications of this process, see: X. Ma, N. Anderson,
L. V. White, S. Bae, W. Raverty, A. C. Willis, M. G. Banwell, Aust. J.
Chem. 2015, 68, 593. doi:10.1071/CH14574
[16] K. C. Nicolaou, D. L. F. Gray, T. Montagnon, S. T. Harrison, Angew.
Chem. Int. Ed. 2002, 41, 996. doi:10.1002/1521-3773(20020315)
41:6,996::AID-ANIE996.3.0.CO;2-I
C16H22O3, M 262.35, T 150 K, orthorhombic, space group
˚
P212121, Z 4, a 8.0668(2), b 9.8097(3), c 18.1236(6) A; V
3
1434.17(7) A , Dx 1.215 g cmꢀ3, 2830 unique data (2ymax
˚
145.48), R 0.032 [for 2698 reflections with I . 2.0s(I)]; Rw
0.088 (all data), S 1.00.
Structure Determinations
Images were measured on a diffractometer (Cu Ka, mirror
˚
monochromator, l 1.54184 A) fitted with an area detector and
the data extracted using the CrysAlis package.[25] The structure
solutions for all four compounds were solved by direct methods
(SIR92)[26] and then refined using the CRYSTALS program
package.[27] Atomic coordinates, bond lengths and angles, and
displacement parameters have been deposited at the Cambridge
Crystallographic Data Centre (CCDC nos. 1832710, 1827734,
1827735, 1827736 and 1827737). These data can be obtained
free-of-charge via www.ccdc.cam.ac.uk/data_request/cif, by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: þ44 1223 336033.
[17] Z. Ma, J. M. Bobbitt, J. Org. Chem. 1991, 56, 6110. doi:10.1021/
JO00021A027
[18] T. Inokuchi, H. Kawafuchi, S. Torii, Chem. Lett. 1992, 1895. doi:10.
1246/CL.1992.1895
[19] G. Y. C. Leung, H. Li, Q.-Y. Toh, A. M.-Y. Ng, R. J. Sum, J. E.
Bandow, D. Y.-K. Chen, Eur. J. Org. Chem. 2011, 183. doi:10.1002/
EJOC.201001281
[20] L. A. Carpino, A. El-Faham, C. A. Minor, F. Albericio, J. Chem. Soc.
Chem. Commun. 1994, 2, 201. doi:10.1039/C39940000201
[21] W. J. Middleton, Org. Synth. 1986, 64, 221. doi:10.15227/ORGSYN.
064.0221
Supplementary Material
The anisotropic displacement ellipsoid plot derived from the
single-crystal X-ray structures of compounds 15/32, 28, 34, 35,
1
and 37 together with the H and/or 13C NMR spectra of com-
pounds 14–20, 25–40, 43–59, 61, and 64 are available on the
Journal’s website.
[22] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923.
doi:10.1021/JO00408A041
Conflicts of Interest
[23] A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen, F. J.
Timmers, Organometallics 1996, 15, 1518. doi:10.1021/OM9503712
[24] See page 1276 in: L. F. Fieser, M. Fieser, Reagents for Organic
Synthesis 1967 (John Wiley and Sons: New York, NY).
[25] CrysAlis PRO Version 1.171.37.35h (release 09-02-2015
CrysAlis171.NET) (compiled 9 February 2015, 16:26:32) (Agilent
Technologies: Oxfordshire, UK).
The authors declare no conflicts of interest.
Acknowledgements
The authors thank the Research School of Chemistry and Institute of
Advanced Studies at the Australian National University for support. The
receipt of an ARC Linkage Grant that underpinned this work is gratefully
acknowledged, as is the provision of an APA(I) to EC. The anti-bacterial
assays were conducted by associates of Dr Alistair Draffan at Biota Holdings
Pty Limited, Melbourne, Australia.
[26] SIR92: A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi,
M. C. Burla, G. Polidori, M. Camalli, J. Appl. Cryst. 1994, 27, 435.
[27] P. W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout, D. J. Watkin,
J. Appl. Cryst. 2003, 36, 1487. doi:10.1107/S0021889803021800