Iran's supreme leader Ayatollah Ali Khamenei on Saturday ruled out any cooperation with the United States in the troubled Middle East, saying talks with Washington are confined to nuclear issues.

In a closely watched speech marking the Persian new year festival of Nowruz, Khamenei took steps to quell speculation that any nuclear deal with the West could lead to a wider rapprochement.

"No way," he told a raucous crowd in the northeastern holy city of Mashhad, on the chances of an agreement on Iran's atomic programme having other policy implications.

"Negotiations with the United States are on the nuclear issue and nothing else," he said.

"US objectives on regional matters are the opposite to our objectives," Khamenei said, accusing Washington of creating instability in Syria, Libya and Egypt.

His remarks were greeted by chants of "Death to America" from the tightly packed thousands who gathered to hear him speak.

Khamenei's comments appeared to be a blunt rejection of overtures made by US President Barack Obama that a nuclear deal could lead to cooperation in the Middle East, chiefly against Islamic State jihadists in Iraq and Syria.

Iran is currently in talks with the United States and other major world powers over ending the 12-year standoff over its disputed nuclear programme.

With time running out on a March 31 deadline for a political deal, the two sides said they remained at odds as negotiations broke up in Lausanne, Switzerland on Friday.

The talks are set to resume on Wednesday.

Khamenei, who spoke for more than an hour, reiterated that Iran wants sanctions lifted under a nuclear deal, backed his negotiating team and called on all Iranians to support the government's aims.

"The lifting of sanctions is part of the negotiations and not the outcome," he said, insisting there could be no delay between the implementation of a deal and the removal of sanctions.

"Sanctions are the only tool that the enemy has against our nation," he added, calling on the country to intensify its domestic economy, stating that relying on foreign help was not a risk worth taking.

Khamenei also dismissed as "insincere" a near five-minute video address for Nowruz that Obama made to the leaders and people of Iran, in which he urged them to choose opportunity over isolation.

He denied a suggestion from Obama that there were people in Iran who did not want a diplomatic solution to the nuclear issue.

"What the Iranian nation does not want is to accept what the Americans want to impose by force," he added. "Officials, our negotiators and the people will not accept it at all."