dehydrative-condensation method and achieving a RuCp/
P(C6H5)3-catalyzed detachment from Jones’ allyl linker. Until
now, it has not been possible to regard APO as a synthetic
target because of the instability of the P–N bond. Although
there is no a-substituent and the final product is still protected,
our new method should inspire further research into the design
and preparation of various phosphorus analogues of
higher peptides, which have high potential in peptide and
nucleotide sciences, and future biochemical technologies.
The characteristics of APOs should make our new type of
unnatural peptide an important complement to existing
unnatural biooligomers.14 The synthesis of unprotected
H-(AlaP(OH))6-OH/DIEA is an on-going project in our group.
Notes and references
y a-Amino phosphonic acid abbreviation follows the IUPAC rule
determined for usual a-amino acids by the addition of ‘‘P’’ at the
end of the three character code. e.g. GlyP for a-aminomethyl phosphonic
acid, where H-GlyP(OH)-OH represents H2NCH2P(O)(OH)2.
1 Book and review: (a) Aminophosphonic and Aminophosphinic Acids,
ed. P. V. Kukhar and R. H. Hudson, Wiley-VCH, Weinheim, 1991,
pp. 1–634; (b) P. Kafarski and B. Lejczak, Phosphorus, Sulfur
Silicon Relat. Elem., 1991, 63, 193–215; (c) The first report on
a-amino phosphonic acids: M. Horiguchi and M. Kandatsu,
Nature, 1959, 184, 901–902.
2 M. Kitamura, M. Yoshimura, M. Tsukamoto and R. Noyori,
Enantiomer, 1996, 1, 281–303.
3 B. P. Morgan, J. M. Scholtz, M. D. Ballinger, I. D. Zipkin and
P. A. Bartlett, J. Am. Chem. Soc., 1991, 113, 297–307.
4 (a) K. Yamauchi, Y. Mitsuda and M. Kinoshita, Bull. Chem. Soc.
Jpn., 1975, 48, 3285–3286; (b) K. Yamauchi, J. Synth. Org. Chem.,
Jpn., 1988, 46, 654–666.
5 R. Hirschmann, K. M. Yager, C. M. Tayor, J. Witherington,
P. A. Sprengeler, B. W. Phillips, W. Moore and A. B. Smith III,
J. Am. Chem. Soc., 1997, 119, 8177–8190.
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4500–4503; (b) K. Yamauchi, S. Ohtsuki and M. Kinoshita, J. Org.
Chem., 1984, 49, 1158–1163; (c) M. Hariharan, R. J. Motekaitis
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(b) L. A. Carpino and A. El-Faham, Tetrahedron, 1999, 55,
6813–6830; (c) L. A. Carpino, H. Imazumi, B. M. Foxman,
M. J. Vela, P. Henklein, A. El-Faham, J. Klose and M. Bienert,
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Fig. 3 The 31Pt{1H} NMR spectrum change during APO elongation
on TentaGel (CDCl3, 25 1C). a: Dimer, b: trimer, c: tetramer,
d: pentamer, e: hexamer. The right-hand spectra show the Fmoc-
deprotected oligomers. K: CH(CHQCH2)(CH2)7CONH-TentaGel.
signals of the terminal phosphonamidates appear at around
d 29, and the chemical shifts are lowered to about d 33 after
Fmoc removal. This phenomenon can be understood by
assuming that the Fmoc moiety has a magnetic shielding
effect, an idea that is consistent with our observations in the
conversion of 3 (d 25.8, 27.0 and 28.0 (50 : 4 : 46))
to H-(GlyP(OBn))2-OBn (d 25.6 and 32.3) in CDCl3.10
10 For details, see the ESIz.
11 (a) R. Greenhalgh, R. M. Heggie and M. A. Weinberger, Can. J.
Chem., 1970, 48, 1351–1357; (b) N. S. Corby, G. W. Kenner and
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Compound
B (n = 6) was subjected to a cationic
12 Y. Hayakawa, S. Wakabayashi, H. Kato and R. Noyori, J. Am.
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13 M. Kitamura, S. Tanaka and M. Yoshimura, J. Org. Chem., 2002,
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RuCp/P(C6H5)3-catalyzed detachment13 (B = 80 mg (0.1 mmol),
S/C = 100, [RuCp catalyst] = 1 mM, [DIEA] = 100 mM,
CH3OH, rt, 24 h, >95% conversion) to give Fmoc-
(GlyP(OBn))6-OH/DIEA (31P NMR: d 19, 29.5 and 31.5;
MALDI-TOF MS: 1360.5 (Fmoc-(GlyP(OBn))6-ONa); tR in
HPLC 3.3 min (column Develosil ODS-UG 4.6 mm ꢂ 25 cm,
eluent 8 : 2–7 : 3 CH3OH–H2O, flow rate 1.0 mL minꢁ1)).
In summary, to the best of our knowledge, a protected
a-amino phosphonic acid hexamer, Fmoc-(GlyP(OBn))6-OH/
DIEA, has been synthesized for the first time by solving
two problems: namely, establishing a DIC/HOAt/DIEA
14 (a) Z. Zhang and E. Fan, J. Org. Chem., 2005, 70, 8801–8810;
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ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 6985–6987 | 6987