solation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

.

Figure 1. Structures of stolonines A-C (1–3), 11-hydroxyascididemin (4) and cnemidine A (5) isolated from the tunicate C. stolonifera.

Table 1. NMR data for 1 in DMSO-d6 a.

Position	δC	δH (J in Hz)	gCOSY	gHMBCAD
1		12.20, br.s	2
2	138.5	8.82, d (3.0)	1	3, 3a, 7a
3	112.1
3a	126.2
4	121.3	8.22, dd (1.8, 7.2)	5	6, 7a
5	122.4	7.24, dt (1.8, 7.2)	4, 6	3a, 7
6	123.3	7.26, dt (1.8, 7.2)	5, 7	4, 7a
7	112.5	7.52, dd (1.8, 7.2)	6	3a, 5
7a	136.2
8	181.6
9	162.7
10		8.78, t (5.4)	11	9
11	35.5	3.50, dd (6.0, 6.6)	10, 12	9, 12
12	49.8	2.66, t (6.6)	11	11

a 1H NMR at 600 MHz referenced to residual DMSO solvent (δH 2.50 ppm) and 13C NMR at 150 MHz referenced to residual DMSO solvent (δC 39.52 ppm).

Stolonine A (1) was obtained as a white amorphous solid. The (−)-HRESIMS spectrum displayed a molecular ion [M−H]−at m/z 295.0390, which was consistent with the molecular formula C12H12N2O5S. The IR spectrum indicated the presence of an S=O stretching band at 1205 cm−1 [16]. A 1H NMR spectrum of 1 showed two exchangeable protons (δH 12.20 and 8.78 ppm), five aromatic protons (δH 8.82, 8.22, 7.52, 7.26 and 7.24 ppm) and two methylenes (δH 3.50 and 2.66 ppm). Further analysis of the 13C NMR and gHSQCAD spectra indicated that the molecule contained two carbonyls (δC 181.6 and 162.7 ppm), eight aromatic carbons (δC 138.5, 136.2, 126.2, 123.3, 122.4, 121.3, 112.5 and 112.1 ppm) and two methylenes (δC 49.8 and 35.5 ppm) (Table 1). J coupling constants of aromatic protons H-4 (δH 8.22, dd, 1.8, 7.2 Hz), H-5 (δH 7.24, dt, 1.8, 7.2 Hz), H-6 (δH 7.26, dt, 1.8, 7.2 Hz) and H-7 (δH 7.52, dd, 1.8, 7.2 Hz) and their COSY correlations were characteristic of a 1,2-disubstituted benzene ring (a, Figure 2). A gCOSY spectrum displayed correlations from the exchangeable proton H-1 (δH12.20, br.s) to H-2 (δH 8.82, d, 3.0 Hz) and also from H-11 (δH 3.50, dd, 6.0, 6.6 Hz) to the triplet exchangeable proton H-10 (δH 8.78, t, 5.4 Hz) and H-12 (δH 2.66, t, 6.6 Hz) facilitating the establishment of two other spin systems, –NH–CH= (b,Figure 2) and –NH–CH2–CH2– (c, Figure 2) respectively. The aromatic carbon C-3 (δC 112.1 ppm) was attached to C-2 (δC138.5 ppm) in the moiety b determined by a HMBC correlation from H-2 to C-3. A HMBC correlation from H-2 to C-7a (δC136.2 ppm) supported the linkage from a to b at C-7a (Figure 2). Both protons H-10 and H-11 in the moiety c showed HMBC correlations with a carbonyl carbon at δC 162.7 ppm suggesting the connection of this carbonyl to N-10 to form an amide bond (c, Figure 2). Two methylene signals at δH 3.50 and 2.66 ppm corresponding to carbons C-11 (δC 35.5 ppm) and C-12 (δC 49.8 ppm) as well as the relatively downfield resonance of the methylene C-12 were diagnostic of methylenes in a taurine moiety (c, Figure 2) [17,18,19].

Table 1. NMR data for 1 in DMSO-d6 a.

Figure 2. Partial structures (a, b and c) of 1 and their key HMBC correlations.

Figure 2. Partial structures (a, b and c) of 1 and their key HMBC correlations.

No HMBC correlation from any proton to the carbonyl C-8 (δC 181.6 ppm) was observed when HMBC experiments were performed and optimized with different JHC couplings. Therefore, two different isomers 1-I and 1-II were conceivable from these data (Figure 3). Detailed HMBC analysis showed that H-2 had a HMBC correlation with C-3a (δC 126.2 ppm). This suggested that 1 was favorable to 1-I since the H-2 to C-3a correlation in 1-I was a three-bond coupling while the H-2 to C-3a correlation in 1-II was a four-bond coupling (Figure 3).

Figure 3. Two possible structures 1-I and 1-II of 1 (1-I and 1-II are possible structural isomers of 1).

Figure 3. Two possible structures 1-I and 1-II of 1 (1-I and 1-II are possible structural isomers of 1).

Table 2. Comparison of experimental and calculated 13C and 1H chemical shifts for 1 in DMSO-d6.

Position	δC (Exp.)	1-I		1-II		δH (Exp.)	1-I		1-II
		δC (Calc.)	δC (Scaled)	δC (Calc.)	δC (Scaled)		δH (Calc.)	δH (Scaled)	δH (Calc.)	δH (Scaled)
2	138.5	136.9	140.3	141.3	142.8	8.82	8.74	8.61	8.84	8.67
3	112.1	111.5	112.9	111.2	110.2
3a	126.2	124.1	126.5	123.0	122.9
4	121.3	118.9	120.9	124.3	124.4	8.22	8.62	8.48	8.40	8.19
5	122.4	120.1	122.1	121.1	120.9	7.24	7.63	7.40	7.63	7.35
6	123.3	120.9	123.0	129.4	129.9	7.26	7.59	7.36	8.00	7.76
7	112.5	108.7	109.9	114.8	114.1	7.52	7.55	7.31	7.53	7.24
7a	136.2	131.9	134.9	134.4	135.3
8	181.6	176.7	183.2	172.5	176.5
9	162.7	156.8	161.7	159.4	162.4
11	35.5	37.1	32.6	36.9	29.8	3.50	3.69	3.11	3.71	3.08
12	49.8	57.2	54.4	58.4	53.1	2.66	3.55	2.95	3.57	2.93
CMAE			1.5		3.1			0.23		0.25
DP4		100.0%		0.0%			85.3%		14.7%

Stolonine A (1): white, amorphous solid; UV (MeOH) λmax (log ε) 210 (3.8), 252 (3.5) and 325 (3.3) nm; IR (film) νmax 3307, 1681, 1205, 1049 and 802 cm−1; 1H (600 MHz, DMSO-d6) and 13C (150 MHz, DMSO-d6) NMR data are summarized in Table 1; (−)-HRESIMS m/z 295.0390 [M − H]− (calcd for [C12H11N2O5S]−, 295.0394, Δ −1.4 ppm).

Mar. Drugs 2015, 13(7), 4556-4575; doi:10.3390/md13074556

Article

Isolation and Total Synthesis of Stolonines A–C, Unique Taurine Amides from the Australian Marine Tunicate Cnemidocarpa stolonifera

Trong D. Tran 1, Ngoc B. Pham 1, Merrick Ekins 2, John N. A. Hooper 1,2 and Ronald J. Quinn 1,*

1

Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland 4111, Australia

2

Queensland Museum, Brisbane, Queensland 4101, Australia

*

Author to whom correspondence should be addressed; Tel.: +61-7-3735-6009; Fax: +61-7-3735-6001.

http://www.mdpi.com/1660-3397/13/7/4556/htm
/////////////////

RAIN FOREST, KODIAK ISLAND, ALASKA, USA
 

HI EVERYONE - YESTERDAY, WE WERE IN THE ROCKY MOUNTAINS.
TODAY, WE ARE GOING TO KODIAK ISLAND IN ALASKA
TO CHECK OUT A RAINFOREST.

IN ORDER TO BE CONSIDERED A RAINFOREST,
IT HAS TO RECEIVE BETWEEN 98 AND 180 INCHES OF
PERCIPITATION, INCLUDING SNOW. ALASKA'S RAINFOREST SANCTUARY IS A
TEMPERATE RAINFOREST, AS OPPOSED TO A TROPICAL RAINFOREST.

KODIAK ISLAND HAS FOUR SEASONS. SPRING HAS A
LOT OF RAIN, CAUSING TREES AND PLANTS TO BLOOM.
SUMMER HAS WARM TEMPERATURES OF 70 - 80 DEGREES FARENHEIT.
AUTUMN HAS COOL TEMPERATURES AND RAIN. WINTER HAS
VERY COLD TEMPERATURES AND SNOW. THE AVERAGE
ANNUAL TEMPERATURE IS 50 DEGREES F.

KODIAK ISLAND'S RAINFOREST RESERVE IS 40 ACRES AND
INCLUDES TALL STANDS OF SPRUCE, HEMLOCK AND
CEDAR TREES WITH A FOREST FLOOR SATURATED WITH MOSSES,
WILD FLOWERS AND A VARIETY OF BERRIES.
THE SANCTUARY IS LOCATED AT PISCURESQUE HERRING COVE.

ON-SITE EXPERIENCES INCLUDE INTERACTING WITH A
HERD OF ALASKAN REINDEER, VISITING THE ALASKA WILDLIFE
FOUNDATION CENTER, WATCHING A NATIVE MASTER TOTEM-POLE
CARVER AT WORK AND VISITING A HISTORIC ALASKAN SAWMILL.
THE ALASKA RAINFOREST SANCTUARY IS A UNIQUE ALASKA
EXPERIENCE AND PERFECT FOR THE NATURE LOVER.
EAGLE CREEK, ONE OF ALASKA'S RICHEST SALMON SPAWNING STREAMS,
FLOWS THROUGH THIS DIVERSE ECOSYSTEM, INTO THE OCEAN.
A MAJOR FISH HATCHERY IS LOCATED ACROSS
THE CREEK FROM THE SANCTUARY BOARDWALK.

I HOPE YOU HAVE ENJOYED YOUR VIST TO
KODIAK ISLAND, ALASKA TO SEE THE RAINFOREST.

RAINFOREST VEGETATION

BROWN BEAR

KODIAK BEAR FAMILY

LORIKEET BIRDS IN RAINFOREST - HARLEQUIN DUCK
 
BLUE GROUSE - CLARK'S NUTCRACKER

KODIAK ISLAND HAS LOTS OF BALD EAGLES

SWORD FERN - WILD STRAWBERRIES

Kodiak Island

Island in Alaska

Kodiak Island is a large island on the south coast of the U.S. state of Alaska, separated from the Alaska mainland by the Shelikof Strait. Wikipedia

 
 Kodiak Municipal Airport, Kodiak Island, Alaska


 

 

 
////////////

Taurine

.

2-aminoethanesulfonic acid

C2 H7 N O3 S

TAURINE

This is an H-NMR of Taurine depicting all peaks.


This is a magnified view of the H-NMR of Taurine. This is a set of two triplet of peaks at 3.38 to 3.42 ppm which corresponds to the “Ha” protons attached to the carbon at the “1” position and at 3.23 to 3.28 ppm which corresponds to the “Hb” protons attached to the carbon at the “2” position. These peaks correspond to the sp3 hybridized hydrogen atoms bonded to the first and second carbon in the compound. There is splitting of the signal in the form of three peaks as the hydrogens are affected by two equavalent adjacent protons present bonded to the first and second carbon; from the N+1 rule, N would then equal 2 for each proton, so N+1, (2+1 = 3), 3 peaks would be observed. The three peaks corresponding to “Ha” deshielded by the electron-withdrawing group SO3H, as well causing a chemical shift to the left. This is so because normally without deshielding an sp3 hydrogen attached to a carbon is around 1.4 ppm. For “Hb” is deshielded by an amine group, which is less electronegative, and therefore less electron withdrawing than the effect seen on “Ha” so it is moved to the left less. The triplet peaks exhibit similar heights because the height of peaks corresponds to the ratio of protons between carbons; since both carbons have two H’s, the ratio is 1:1, so their heights are similar.





This is the C-NMR spectra of Taurine depicting all peaks.


This is a magnified view of the C-NMR of Taurine. It depicts a single peak from 50.1-50.23ppm and corresponding to the first carbon bonded to both the sulfur as well as the second carbon. The reason why the C-NMR would correspond to 50.1-50.23 is because the H-NMR corresponding to the protons attached to Carbon #1 is around 3.4 ppm. Since C-NMR peaks represent 15-20 times the amount of ppm of the protons attached to it, 3.4 x 15 is approximately 51 ppm. (See above explanation for H-NMR peak at 3.4 ppm)



This is a magnified view of the C-NMR of Taurine. There is a single peak at approximately 38.20 ppm, which corresponds to the second carbon bonded to the nitrogen group. The reason why the C-NMR would correspond to 38.2 is because the H-NMR corresponding to the protons attached to Carbon #2 is around 3.2 ppm. Since C-NMR peaks represent approximately 15-20 times the amount of ppm of the protons attached to it, 3.2 x 15 is approximately 48 ppm. (See above explanation for H-NMR peak at 3.2 ppm). Although the peak doesn’t exactly match with the H-NMR prediction, it can be deduced that this C-NMR peak correlates with Carbon #2 because it is the lesser ppm of the two C-NMR peaks.

2D [1H,1H]-TOCSY

1D DEPT90

1D DEPT135

2D [1H,13C]-HSQC

2D [1H,13C]-HMBC

///////////

MT. MC KINLEY, DENALI, ALASKA, USA

Denali

Mountain in Alaska

Denali /dᵻˈnɑːli/ is the highest mountain peak in North America, with a summit elevation of 20,310 feet above sea level. At some 18,000 ft, the base-to-peak rise is the largest of any mountain situated entirely above sea level. Wikipedia

HI EVERYONE. YESTERDAY, WE WERE AT THE GATEWAY ARCH IN
ST. LOUIS, MISSOURI. TODAY WE ARE TAKING A BIG TRIP,
BACK TO ALASKA. I KNOW WE WERE THERE BEFORE BUT
THERE IS MORE TO SEE THERE. THIS TRIP IS GOING
TO TAKE IN ALL KINDS OF SIGHTS.

WE ARE GOING TO START OUT IN A BOAT ON
LAKE WONDER. AS WE TRAVEL ON THE BOAT, WE WILL
SEE ALDER AND WILLOW CARPETED HILLS ALONG WITH SOME SMALLER
PONDS. KEEP YOUR EYES OPEN CAUSE THERE IS A LOT OF
WATERFOWL AND OTHER WILDLIFE AROUND.

SOMETHING THAT WON'T BE HARD TO SEE IS THE STUNNING
VIEW OF MOUNT MCKINLEY AND THE ALASKA RANGE. MT. MCKINLEY
IS THE HIGHEST MOUNTAIN PEAK IN NORTH AMERICA, WITH A
SUMMIT ELEVATION OF 20,320 FEET ABOUT SEA LEVEL. YOU WILL
SEE SNOW ON THE MOUNTAIN TOP AT ANY TIME OF
THE YEAR. THERE ARE FIVE LARGE GLACIERS THAT FLOW OFF
THE SLOPES OF THE MOUNTAIN. LAKE WONDER THAT WE ARE
TRAVELING ON WAS CREATED BY RETREATING GLACIERS. IF ANYONE
IS ENERGENIC, YOU CAN HIKE THE MOUNTAIN.

I HOPE YOU ENJOYED YOUR RIDE ON THE BOAT WITH
THE SPECTACULAR VIEWS OF THE MOUNTAINS AND WILDLIFE...

 

 

 

 

 

 

 
 

 
 
//////////

2-Hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-3-((2-(trifluoromethyl)phenyl)thio)propanamide

2-Hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-3-((2-(trifluoromethyl)phenyl)thio)propanamide 

Purified by flash column chromatography eluting with n-hexane/EtOAc 100:0 v/v increasing to n-hexane/EtOAc 70:30 v/v. Obtained in 57% yield as a pale yellow sticky solid. 

¹H-NMR (CDCl₃): d 9.00 (bs, 1H), 7.93-7.90 (m, 2H), 7.72-7.69 (m, 2H), 7.49-7.46 (m, 2H), 7.24-7.21 (m, 1H), 4.00 (d, J= 14.3 Hz, 1H), 3.57 (s, 1H), 3.21 (d, J= 14.3 Hz, 1H), 1.57 (s, 3H). 

¹⁹F-NMR (CDCl₃): d -60.17 (s, 3F), -60.07 (s, 3F).

¹³C-NMR (CDCl₃): d 172.7, 141.0, 134.0, 132.6, 132.3, 127.4, 126.7, 126.6, 126.6, 122.7, 121.8, 118.0, 117.9, 75.1, 45.3, 26.1. 

MS [ESI, m/z]: 469.3 [M+H]⁺, 491.0 [M+Na]⁺.

 EI-HMRS (M-H)^- found 467.0489, calculated for C₁₈H₁₃N₂O₄F₆S 467.0500. 

HPLC (method 1): retention time = 22.44 min.

¹H-NMR (CDCl₃): d 9.00 (bs, 1H), 7.93-7.90 (m, 2H), 7.72-7.69 (m, 2H), 7.49-7.46 (m, 2H), 7.24-7.21 (m, 1H), 4.00 (d, J= 14.3 Hz, 1H), 3.57 (s, 1H), 3.21 (d, J= 14.3 Hz, 1H), 1.57 (s, 3H). 

1H NMR

¹⁹F-NMR (CDCl₃): d -60.17 (s, 3F), -60.07 (s, 3F).

¹⁹F-NMR

¹³C-NMR (CDCl₃): d 172.7, 141.0, 134.0, 132.6, 132.3, 127.4, 126.7, 126.6, 126.6, 122.7, 121.8, 118.0, 117.9, 75.1, 45.3, 26.1. 

¹³C-NMR

Dr Marcella Bassetto

Post Doctoral Research Associate

bassettom@cardiff.ac.uk

https://www.researchgate.net/profile/Marcella_Bassetto

http://marcellabassetto.blogspot.in/

Cardiff University

School of Pharmacy and Pharmaceutical Sciences

Cardiff, Wales, United Kingdom

Paper

European Journal of Medicinal Chemistry

Volume 118, 8 August 2016, Pages 230–243

Research paper

Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer

School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edward VII Avenue, CF10 3NB, Cardiff, Wales, UK

This work is dedicated to the memory of Prof. Chris McGuigan, a great colleague and scientist, invaluable source of inspiration and love for research.

• Marcella Bassetto1,
• Salvatore Ferla, 1, ,
• Fabrizio Pertusati1,
• Sahar Kandil,
• Andrew D. Westwell,
• Andrea Brancale,
• Christopher McGuigan

doi:10.1016/j.ejmech.2016.04.052

E-mail address: Ferlas1@cardiff.ac.uk (Dr. S. Ferla)

---

Highlights

•Synthesis of novel fluorinated bicalutamide and enzalutamide analogs.

•Anti-proliferative activity in four human prostate cancer cell lines improved up to 50 folds.

•Full AR antagonist effect exhibited by the new compounds.

•Activity switch from partial agonist to full AR antagonist for enobosarm scaffold.

•AR open conformation homology model and molecular modeling studies.

---

Abstract

Prostate cancer (PC) is one of the major causes of male death worldwide and the development of new and more potent anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the case of castration-resistant forms. Both these drugs present a moderate antiproliferative activity and their use is limited due to the development of resistant mutants of their biological target.

Insertion of fluorinated and perfluorinated groups in biologically active compounds is a current trend in medicinal chemistry, applied to improve their efficacy and stability profiles. As a means to obtain such effects, different modifications with perfluoro groups were rationally designed on the bicalutamide and enzalutamide structures, leading to the synthesis of a series of new antiproliferative compounds. Several new analogues displayed improved in vitro activity towards four different prostate cancer cell lines, while maintaining full AR antagonism and therefore representing promising leads for further development.

Furthermore, a series of molecular modelling studies were performed on the AR antagonist conformation, providing useful insights on potential protein-ligand interactions.

http://www.sciencedirect.com/science/article/pii/S0223523416303452

Top cancer scientist dies of the disease he spent his life trying to cure

Professor Chris McGuigan, 57, of Cardiff University, was trying to invent new drugs to use in the fight against the disease

A university spokesman described Prof McGuigan as ‘exceptionally gifted’

A top cancer scientist has died from the disease – after a lifetime of research looking for a cure.

Professor Chris McGuigan, 57, was trying to invent new drugs to use in the fight against the disease.

But the tragic scientist, who was head of medicinal chemistry at Cardiff University’s School of Pharmacy and Pharmaceutical Sciences, died after his own fight with cancer.

A spokesman for Cardiff University said: “Professor McGuigan had been at the heart of scientific research for more than 30 years. He was an exceptionally gifted inventor and chemist.

“His loss will be felt cross the university and the wider scientific community.

South Wales Echo

Prof McGuigan invented four new experimental drugs that were used in human clinical trials

“He had a strong drive to use his scientific ideas for social good, working tirelessly to address medical needs where they were unmet.

“Our thoughts are with his family, friends and close colleagues at this very sad time.”

Prof McGuigan’s research led him to try and develop new drugs for cancer, HIV, hepatitis B and C, shingles, measles, influenza and central nervous system (CNS) disease.

He also invented four new experimental drugs that were used in human clinical trials.

Prof McGuigan, who lived in Cardiff, is survived by wife Maria, 50, and his two young daughters Phoebe and Grace.

/////////

Rifaximin

Rifaximin;
Rifaxidin; Rifacol; Xifaxan; Normix; Rifamycin L 105;L 105 (ansamacrolide antibiotic), L 105SV
(2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S,28E)-5,6,21,23,25-pentahydroxy-27-methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7-(epoxypentadeca-[1,11,13]trienimino)benzofuro[4,5-e]pyrido[1,2-á]-benzimidazole-1,15(2H)-dione,25-acetate
 CAS 80621-81-4,  4-Deoxy-4-methylpyrido[1,2-1,2]imidazo[5,4-c]rifamycin SV,
4-Deoxy-4′-methylpyrido[1′,2′-1,2]imidazo[5,4-c]rifamycin SV, Rifacol

C43H51N3O11
Molecular Weight:	785.87854 g/mol

XIFAXAN tablets for oral administration are film-coated and contain 200 mg or 550 mg of rifaximin.

See synthesis
http://www.allfordrugs.com/2016/07/06/rifaximin/



SPECTRA
LINK IS CLICK

APT 13C NMR RIFAXIMIN

1H NMR PARTIAL

IR



Direct infusion mass analysis ESI (+)




IH NMR

• [-]ESI    FRAG PATHWAY

PATENT

Patent US20130004576
Rifaximin (INN; see The Merck Index, XIII Ed., 8304, CAS no. 80621-81-4), IUPAC nomenclature (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S,28E)-5,6,21,23,25 pentahydroxy-27-methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7-(epoxypentadeca-(1,11,13)trienimino)benzofuro(4,5-e)pyrido(1,2,-a)benzimidazole-1,15(2H)-dione,25-acetate) is a semi-synthetic antibiotic belonging to the rifamycin class of antibiotics. More precisely rifaximin is a pyrido-imidazo rifamycin described in the Italian patent IT 1154655, whereas the European patent EP 0161534 discloses a process for rifaximin production using rifamycin O as starting material (The Merck Index, XIII Ed., 8301).
U.S. Pat. No. 7,045,620, US 2008/0262220, US 7,612,199, US 2009/0130201 and Cryst. Eng. Comm., 2008, 10 1074-1081 (2008) disclose new forms of rifaximin.
WO 2008/035109 A1 discloses a process to prepare amorphous rifaximin, which comprises reaction of rifamycin S with 2-amino-4 picoline in presence of organic solvent like dichloromethane, ethylacetate, dichloroethylene, chloroform, in an inert atmosphere. When water is added to the reaction mixture, a solid precipitate corresponding to amorphous rifaximin is obtained.
The process described in this document can be assimilated to a crash precipitation, wherein the use of an anti-solvent causes the precipitation of rifaximin without giving any information about the chemical physical and biological characteristics of the rifaximin obtained.
WO 2009/108730 A2 describes different polymorphous forms of rifaximin and also amorphous forms of rifaximin. Amorphous forms are prepared by milling and crash precipitation and with these two different methods the amorphous rifaximin obtained from these two different processes has the same properties.

FIG. 4: ¹³C-NMR spectrum of rifaximin obtained by spray drying process.

FIG. 5: FT-IR spectrum of rifaximin obtained by spray drying process.

/////////
See synthesis
http://www.allfordrugs.com/2016/07/06/rifaximin/