ization of hemiacetal 13. Intermediate 13 could be ob-
tained by assembling lactone 2 (C5-C11) and alkyne 3
(C12-C15).
Scheme 3. Synthesis of Alkyne 3
Scheme 2. Synthesis of Lactone 2
for 12 h followed by quenching of the ethylmagnesation
product with O2 resulted in the formation of alcohol 9 (72%)
as a single diastereomer. Though terminal alkenes are not
subject to strict conformational control, exclusive formation
of the diastereomer is due to bulky cyclohexylidene protec-
tion adjacent to the site of addition in olefin 8. Having
successfully installed the C14 ethyl center using an efficient
protocol, we next proceeded to synthesize the alkyne
functionality by oxidation of alcohol 9 with BAIB-TEMPO
to afford aldehyde 10 (91% yield), which was converted to
alkyne 3 (72%) by employing Ohira-Bestmann reagent.13
As our initial objective to synthesize the pteridic acid A
through the assemble of the lactone 2 with vinyl iodide 11
(prepared from aldehyde 10 using Stork and Zhao protocol)
using n-BuLi and i-PrMgBr14 met with failure and ended
up with doubly vinylated product (in minor quantities) along
with unsaturated lactone (in major quantities). When we tried
the coupling by transmetalation of Li to Mg using t-BuLi-
As outlined in Scheme 2, the C5-C11 segment 2 was
prepared mainly on the basis of desymmetrization of bicyclic
olefin using Brown’s chiral hydroboration via known triol
4, which was extensively utilized as a building block for
the synthesis of many natural products containing polypro-
pionate units in our laboratory.7 Synthesis of lactone 2 was
commenced with the conversion of triol 4 to acetal 5 using
anisaldehyde dimethyl acetal8 and catalytic CSA. Reductive
opening of acetal with NaBH3CN9 led to the 1,5-diol 6 (71%
yield). The resulting 1,5-diol was subjected to oxidative
lactonization in the presence of BAIB-TEMPO10 to obtain
lactone 7 (87% yield). Epimerization of lactone 7 at the C2
position by exposure to a stoichiometric amount of DBU7b
completed the construction of the key Prelog-Djerassi-type
lactone 2.
15
MgBr2 at -136 °C (Liq N2-pentane bath), it resulted in
dehydrohalogenation of vinyl iodide along with unreacted
lactone (Scheme 4).
The failures of our initial attempts forced us to revise the
coupling strategy (Scheme 5) in which the alkyne 3 was
chosen as a coupling partner. Thus, treatment of lactone 2
with lithium acetylide16 of 3 at -78 °C afforded lactol.
Exposure of this crude lactol to a catalytic amount of CSA
in MeOH resulted in the formation of hemiacetal 12 with
concomitant deprotection of the cyclohexylidene acetal.
Next the hemiacetal 12 was subjected to partial hydroge-
nation using Lindlar’s catalyst to establish the Z-alkene
functionality in 13 (92%). Our next key task en route to the
synthesis of pteridic acid A, spiroketalization was achieved
under mild acidic conditions. To our delight, the NMR
The synthesis of the C12-C15 segment (Scheme 3) began
with the installation of the crucial ethyl center at C14 by
employing a zirconium-catalyzed carbomagnesation protocol
developed by Hoveyda.11 Thus the treatment of olefin12
8
with EtMgCl and 5 mol % of Cp2ZrCl2 at room temperature
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