Measurement of pH is of great importance because it usually plays a

vital role in a variety of systems. The design and synthesis of fluorescent

molecules for measurement of pH is well established due to the simplicity,
high sensitivity and high spatial resolution of fluorescence.

Organic dyes are the most widely used fluorescent probes for
indication of pH. However, most of these fluorescent dyes have poor
solubility in water and the hydrophobicity greatly limits their applications.
Therefore there is still plenty of room to develop indicators for measurement
pH in 100% aqueous system.

Among the most studied chromophores for construction pH probes,
boron-dipyrromethene (BODIPY) fluorescent dyes have been recognized as
the promising ones because of their excellent characteristics.
BODIPYs bearing receptors for H
+
at 8- positon showed
deprotonation/protonation dependent fluorescence off/on switching. These
probes reported respond to H with just fluorescent turn-on signal.
Unfortunately, single-intensity-based sensing is compromised by the local
distribution of probes, drifts of light sources and detectors.

Ratiometric fluorescent probes that can overcome the limitation of
intensity-based probes and provide quantitative measurement are therefore
in demand. To measure pH by a ratiometric and fluorometric method, the
indicator should ideally be fluorescent and exhibit spectroscopic shifts with
changing pH value.

Very recently, this group developed a 6-hydroxyindole-based
BODIPY with straightforward phenol/phenolate interconversion by varying
pH value, showing phenol/phenolate dependent emission blue-red
switching
Therefore, this BODIPY can be an excellent ratiometric pH indicator
in aqueous-organic mixed media. However, the neutral form of 6-
hydroxyindole-based BODIPY is nonfluorescent and unstable in complete
aqueous systems.

With the idea of developing new ratiometric fluorescent probes for
indication of pH in 100% aqueous system, herein we introduce a simple and
general route to encapsulate 6-hydroxyindole-based BODIPYs into water
soluble surfactant micelles for sensing pH.

In this work was select the cetyltrimethylammonium bromide
(CTAB) micelle, containing a positively charged surface and a hydrophobic
interior microheterogeneous environment. They demonstrate the
hydrophobic BODIPYs 1 and 2 can be physically trapped inside the
hydrophobic core while ensuring solubility in water.
Due to the hydrophobic character of the micelles core, 1 and 2
therefore become fluorescent with high quantum yields in aqueous system
as they behave in organic solvents. As expected, both 1 and 2 trapped in
CTAB micelles display ratiometric optical change within the pH window of
4-9, accompanied with distinct color change.
65%
22%
No se observan diferencias significativas del espectro de absorcin en disolventes
con diferente polaridad.
Propiedades espectroscpicas
S
0
-S
1
540-559 nm 567-580 nm
540 nm
626 nm
Punto isobstico en 562 nm
Desplazamiento al rojo en 86 nm
567 nm
658 nm
Desplazamiento al rojo en 91 nm
Cambio en el color de
fluorescencia de amarillo a
salmn oscuro bajo luz UV
Respuesta ratiomtrica al pH en solucin acuosa
576 nm
645 nm
620 nm
Punto de isoemisin en 620 nm
Proceso reversible
pKa = 9.1 y pKa*=3.7
Este fenmeno ratiometrico desaparece al
aumentar la relacin de agua.
1 y 2 son poco solubles en agua, pero se disuelven fcilmente en
presencia de CTBA. Un sistema de micelas estables se prepar al agregar una
solucin micelar de CTAB en agua (10 mL, 2.0 mm) a un vial con 1 o 2 bajo
agitacin vigorosa.

Al igual que en disolventes orgnicos, los correspondientes
espectros de absorcin de los BODIPYs, dentro de las micelas en disolucin
acuosa muestran las bandas caractersticas del fluoroforo con una banda de
absorcin en 558 nm y 555 nm para 1 y 2 respectivamente. En el espectro de
emisin se observa una banda en 587 nm para ambos.

Con esto se pudieron evaluar sus propiedades espectroscpicas
dependientes del pH teniendo como disolvente agua.
558 nm
629 nm
555 nm
Punto isobstico en 576 nm, esto es evidencia de que existe un
equilibrio entre la forma fenolica y el fenolato entre el rango de pH
de 4-9.
1 y 2 en
micelas fluorescen
de color naranja
cerca de 587 nm a
valores de pH
bajos.

Punto de
isoemisin en 630
nm. Esto
demuestra la
capacidad de 1 y 2
como indicadores
fluorescentes
ratiometricos de
pH en agua. El
intervalo de
estudio incluye al
rango de pH
fisiologico.
The fluorescence intensity
ratio (I
650
/I
587
) of (a) 1 and (b) 2 in
CTAB micelles solutions in the
absence and presence of cations at pH
7.64. (a) free micelles solution, (b)
Na
+
, (c) K
+
, (d) Li
+
, (e) Cs
+
, (f) Fe
2+
, (g)
Mn
2+
, (h) Mg
2+
, (i) Pb
2+
, (j) Zn
2+
, (k)
Hg
2+
, (l) Cu
2+
.
Estudio frente a iones de relevancia biolgica
The fluorescence intensity
ratio (I
650
/I
587
) of (a) 1 and (b) 2 in
CTAB micelles solutions in the
absence and presence of biological
relevant ions at pH 7.64. (a) free
micelles solution, (b) SO
3
2-
, (c) PO
4
3-
,
(d) Cys, (e) Tyr, (f) Glu, (g) Lys, (h)
Thr.
Estudio frente a iones y pequeas molculas bioactivas
El cambio de coloracin
es rpido y puede ser repetido por
muchos ciclos con el mismo
comportamiento espectral, lo cual
sugiere que el proceso de
protonacin y desprotonacin es
muy reversible.
1. Se comprob que 1 y 2 pueden ser atrapados dentro del interior
hidrofobico de micelas de CTAB en agua.
2. Dentro de la micela 1 y 2 mantienen sus propiedades fotofsicas.
3. Estas micelas presentan un respuesta sensible a cambios de pH por
ratiometria en agua.
4. El proceso es reversible y se puede repetir por varios ciclos.
5. Todo esto indica que estos BODIPYs pueden usarse como indicadores
fluorescentes ratiometricos de pH en el rango de 4-9 en sistemas
acuosas.

Not only due to its potent analgesic effect but also because of its
complex molecular architecture, (-)-morphine (1) is one of the most
interesting and most thoroughly investigated alkaloids. Since millennia
humans have used opium, which contains morphine, to alleviate pain.
In the search for morphine derivatives with reduced side effects,
total synthesis offers an attractive opportunity although an economical
route competitive to isolation is currently not within reach.
Several efforts in the recent past, for example, the elegant
synthesis by Magnus, [1] the improved strategy of Fukuyama,[2] the
chemoenzymatic approach of Hudlicky,[3] and the innovative route of
Stork,[4] express the permanent interest of the scientific community

[1] P. Magnus, N. Sane, B. P. Fauber, V. Lynch, J. Am. Chem. Soc. 2009, 131, 16045 16047.
[2] T. Fukuyama, S. Yokoshima, T. Kan, K. Uchida, Org. Lett. 2006, 8, 5311 5313.
[3] T. Hudlicky, H. Leisch, A. T. Omori, K. J. Finn, J. Gilmet, T. Bissett, D. Ilceski, Tetrahedron 2009, 65, 9862 9875.
[4] G. Stork, A. Yamashita, J. Adams, G. R. Schulte, R. Chesworth, Y. Miyazaki, J. J. Farmer, J. Am. Chem. Soc. 2009,
131, 11402 11406.
Cicloadicin intramolecular de
una nitrona, para la construccin
del fenantreno. El p-quinol ter
acta como dipolarofilo.
5

[5] P. J. Parsons, M. Chandler, J. Chem. Soc. Chem. Commun. 1984, 322 323
En 4 el C9 y C14 tendrn la
conformacin relativa correcta. El
reordenamiento de Claisen
formara el C cuaternario y el
carbociclo.
6

[6] A. M. M. Castro, Chem. Rev. 2004, 104, 2939 3002
Alquilacin transanular de la
amina secundaria liberada de la
reduccin de la nitrona.
7

[7] M. Bols, O. L. Lopez, J. G. Fernndez-Bolaos, V. H. Lillelund, Org. Biomol. Chem. 2003, 1, 478 482.
Sustitucin alilica,
8
seguido de
una transposicin alilica, en la
cual el OH pasa de C8 a C6.
Para obtener la codeina (2).
[8] D. F. Taber, T. D. Neubert, A. L. Rheingold, J. Am. Chem. Soc. 2002, 124, 12416 12417.
15: allopseudomorfina
16: allopseudocodeina
Se desarrollo una ruta sencilla a partir de la isovanilin a (6) a la
allopseudocodeina (16) como parte de una sntesis total y dos sntesis
formales del alcaloide objetivo (2).

Varios pasos cruciales como la cicloadicin intramolecular de la
nitrona y el reordenamiento de Claisen permitieron la construccin de
manera fcil del ncleo de la morfina.

Falta optimizar la reaccin de la transposicin alilica final en la
reraccin.
Amitabh Jha, ARKIVOC, 2006, (i), 13-20
Acetal amida Alcohol alilico